CHD7
chromodomain helicase DNA binding protein 7, the group of Myb/SANT domain containing|DNA helicases
Basic information
Region (hg38): 8:60678739-60868028
Previous symbols: [ "CRG" ]
Links
Phenotypes
GenCC
Source:
- CHARGE syndrome (Strong), mode of inheritance: AD
- CHARGE syndrome (Definitive), mode of inheritance: AD
- CHARGE syndrome (Supportive), mode of inheritance: AD
- Kallmann syndrome (Supportive), mode of inheritance: AD
- hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
- Omenn syndrome (Supportive), mode of inheritance: AR
- CHARGE syndrome (Strong), mode of inheritance: AD
- hypogonadotropic hypogonadism 5 with or without anosmia (Strong), mode of inheritance: AD
- CHARGE syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| CHARGE syndrome; Hypogonadotropic hypogonadism 5 with or without anosmia | AD | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal; Genitourinary | In CHARGE syndrome, awareness of the potential for cardiovascular, renal, and genitourinary manifestations may allow surveillance and prompt treatment, and awareness of the risk of infections (T-cell abnormalities have been described in some individuals) may benefit efficient treatment of infectious sequelae; Awareness of the risk of hearing impairment may allow prompt detection and treatment aimed at speech and language development; In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Renal; Genitourinary | 15300250; 16155193; 16400610; 17661815; 7334995; 17937444; 17684005; 18241060; 18074359; 18834967; 18978652; 18445044; 9375527; 19021638; 20301509; 22724017; 25985275 |
ClinVar
This is a list of variants' phenotypes submitted to
- CHARGE association (2183 variants)
- not provided (958 variants)
- Inborn genetic diseases (428 variants)
- Hypogonadotropic hypogonadism 5 with or without anosmia (224 variants)
- not specified (186 variants)
- CHARGE association;Hypogonadotropic hypogonadism 5 with or without anosmia (150 variants)
- Hypogonadotropic hypogonadism 5 with or without anosmia;CHARGE association (84 variants)
- CHD7-related condition (59 variants)
- Hypogonadism with anosmia (22 variants)
- See cases (6 variants)
- Amenorrhea (5 variants)
- Intellectual disability (4 variants)
- Hearing impairment (4 variants)
- Neurodevelopmental disorder (2 variants)
- Bilateral hearing loss, bilateral enlarged vestibular aqueduct (EVA) (2 variants)
- Childhood onset hearing loss (2 variants)
- CHD7 disorder (1 variants)
- Hypogonadotropic hypogonadism (1 variants)
- CHD7-related disorder (1 variants)
- Developmental disorder (1 variants)
- Congenital heart disease (variable) (1 variants)
- Iris coloboma (1 variants)
- Hearing impairment;Ventricular septal defect (1 variants)
- Pituitary stalk interruption syndrome (1 variants)
- CHD7-related disorders (1 variants)
- Premature ovarian failure (1 variants)
- Primary dilated cardiomyopathy (1 variants)
- Pyloric stenosis;Atrial septal defect;Abnormal facial shape;Choanal atresia (1 variants)
- Autism spectrum disorder (1 variants)
- Familial atrioventricular septal defect (1 variants)
- 6 conditions (1 variants)
- 3MC syndrome (1 variants)
- Pulmonary artery atresia;Hearing impairment;Chorioretinal coloboma;Retinal coloboma (1 variants)
- Scoliosis, isolated, susceptibility to, 3 (1 variants)
- Pure gonadal dysgenesis 46,XY (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHD7 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 461 | 27 | 508 | ||
| missense | 11 | 38 | 864 | 154 | 83 | 1150 |
| nonsense | 170 | 15 | 185 | |||
| start loss | 0 | |||||
| frameshift | 246 | 32 | 278 | |||
| inframe indel | 26 | 32 | ||||
| splice donor/acceptor (+/-2bp) | 40 | 24 | 66 | |||
| splice region ? | 6 | 10 | 30 | 50 | 3 | 99 |
| non coding ? | 63 | 201 | 85 | 353 | ||
| Total | 470 | 114 | 974 | 818 | 196 |
Highest pathogenic variant AF is 0.00000657
Variants in CHD7
This is a list of pathogenic ClinVar variants found in the CHD7 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-60678764-C-CGCG | CHARGE syndrome • Hypogonadism with anosmia | Uncertain significance (Jun 14, 2016) | ||
| 8-60678764-C-CGCGGCG | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678776-G-A | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 12, 2018) | ||
| 8-60678785-G-A | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 13, 2018) | ||
| 8-60678785-GGCGGCA-G | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678788-G-A | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 12, 2018) | ||
| 8-60678788-G-GGCGGCA | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-G | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 13, 2018) | ||
| 8-60678791-A-GGCGGCGGCGGCG | CHARGE syndrome • Hypogonadism with anosmia | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-GGCGGCGGCG | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-GGCGGCGGCGGCGGCGGCG | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-GGCGGCGGCGGCGGCGGCGGCGGCG | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-GGCGGCGGCGGCGGCGGCGGCG | CHARGE syndrome • Hypogonadism with anosmia | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-GGCGGCGGCGGCAGCG | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-GGCGGCAGCG | CHARGE syndrome • Hypogonadism with anosmia | Uncertain significance (Jun 14, 2016) | ||
| 8-60678791-A-AGCG | Hypogonadism with anosmia • CHARGE syndrome | Uncertain significance (Jun 14, 2016) | ||
| 8-60678877-C-T | Hypogonadotropic hypogonadism 5 with or without anosmia | Benign (Jan 12, 2018) | ||
| 8-60678930-C-G | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 12, 2018) | ||
| 8-60678959-C-A | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 13, 2018) | ||
| 8-60679008-C-G | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 13, 2018) | ||
| 8-60679027-G-C | Hypogonadotropic hypogonadism 5 with or without anosmia | Conflicting classifications of pathogenicity (May 01, 2023) | ||
| 8-60679076-C-G | Hypogonadotropic hypogonadism 5 with or without anosmia | Uncertain significance (Jan 13, 2018) | ||
| 8-60679082-G-A | Uncertain significance (Apr 24, 2023) | |||
| 8-60740951-G-A | Likely benign (Aug 08, 2018) | |||
| 8-60741037-T-C | Benign (Sep 22, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CHD7 | protein_coding | protein_coding | ENST00000423902 | 37 | 188129 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.82e-19 | 124648 | 0 | 9 | 124657 | 0.0000361 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.22 | 1254 | 1.62e+3 | 0.775 | 0.0000910 | 19709 |
| Missense in Polyphen | 365 | 653.16 | 0.55882 | 7696 | ||
| Synonymous | -0.809 | 637 | 612 | 1.04 | 0.0000367 | 5740 |
| Loss of Function | 10.5 | 5 | 138 | 0.0363 | 0.00000803 | 1592 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000292 | 0.000287 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000268 | 0.0000265 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000654 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Probable transcription regulator. Maybe involved in the in 45S precursor rRNA production. {ECO:0000269|PubMed:22646239}.;
- Disease
- DISEASE: Idiopathic scoliosis 3 (IS3) [MIM:608765]: An abnormality of the vertebral column in which patients develop lateral curvature of the spine of at least 10 degrees. {ECO:0000269|PubMed:17436250}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Hypogonadotropic hypogonadism 5 with or without anosmia (HH5) [MIM:612370]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:18834967, ECO:0000269|PubMed:21158681, ECO:0000269|PubMed:25077900}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Noncanonical Wnt signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.140
Intolerance Scores
- loftool
- 0.0283
- rvis_EVS
- -2.92
- rvis_percentile_EVS
- 0.57
Haploinsufficiency Scores
- pHI
- 0.142
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.566
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.905
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Chd7
- Phenotype
- craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;
Zebrafish Information Network
- Gene name
- chd7
- Affected structure
- microvillous olfactory receptor neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- skeletal system development;in utero embryonic development;blood vessel remodeling;heart morphogenesis;ventricular trabecula myocardium morphogenesis;right ventricular compact myocardium morphogenesis;chromatin remodeling;regulation of transcription, DNA-templated;rRNA processing;central nervous system development;adult heart development;sensory perception of sound;adult walking behavior;blood circulation;response to bacterium;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;cranial nerve development;olfactory nerve development;olfactory bulb development;T cell differentiation;female genitalia development;embryonic hindlimb morphogenesis;aorta morphogenesis;atrioventricular canal development;positive regulation of multicellular organism growth;olfactory behavior;inner ear morphogenesis;nose development;positive regulation of transcription by RNA polymerase II;semicircular canal morphogenesis;genitalia development;regulation of neurogenesis;cognition;retina development in camera-type eye;regulation of growth hormone secretion;limb development;face development;innervation;cardiac septum morphogenesis;epithelium development;secondary palate development
- Cellular component
- nucleus;nucleoplasm;nucleolus
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;chromatin binding;helicase activity;protein binding;ATP binding;promoter-specific chromatin binding