CHD7

chromodomain helicase DNA binding protein 7, the group of Myb/SANT domain containing|DNA helicases

Basic information

Region (hg38): 8:60678740-60868028

Previous symbols: [ "CRG" ]

Links

ENSG00000171316 ∙ NCBI:55636 ∙ OMIM:608892 ∙ HGNC:20626 ∙ Uniprot:Q9P2D1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CHARGE syndrome (Definitive), mode of inheritance: AD
• CHARGE syndrome (Strong), mode of inheritance: AD
• hypogonadotropic hypogonadism 5 with or without anosmia (Strong), 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 (Definitive), mode of inheritance: AD
• CHARGE syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the CHD7 gene.

• CHARGE_syndrome (3360 variants)
• not_provided (1196 variants)
• Inborn_genetic_diseases (671 variants)
• Hypogonadotropic_hypogonadism_5_with_or_without_anosmia (649 variants)
• CHD7-related_disorder (254 variants)
• not_specified (217 variants)
• CHD7-related_CHARGE_syndrome (12 variants)
• See_cases (8 variants)
• Intellectual_disability (8 variants)
• Amenorrhea (6 variants)
• Hypogonadism_with_anosmia (6 variants)
• Hearing_impairment (5 variants)
• 3-Oxo-5_alpha-steroid_delta_4-dehydrogenase_deficiency (3 variants)
• Hypogonadotropic_hypogonadism (2 variants)
• Neurodevelopmental_disorder (2 variants)
• Bilateral_hearing_loss,_bilateral_enlarged_vestibular_aqueduct_(EVA) (2 variants)
• Childhood_onset_hearing_loss (2 variants)
• Congenital_heart_disease (1 variants)
• Pituitary_stalk_interruption_syndrome (1 variants)
• Autism_spectrum_disorder (1 variants)
• Progressive_hearing_impairment (1 variants)
• Microcephaly (1 variants)
• Primary_dilated_cardiomyopathy (1 variants)
• Scoliosis (1 variants)
• Structural_eye_disease (1 variants)
• Poor_coordination (1 variants)
• 3MC_syndrome (1 variants)
• Choanal_atresia (1 variants)
• Retinal_coloboma (1 variants)
• Dolichocephaly (1 variants)
• Cystic_fibrosis (1 variants)
• Isolated_anophthalmia-microphthalmia_syndrome (1 variants)
• Dystonia,_early-onset,_and/or_spastic_paraplegia (1 variants)
• 46,XY_disorder_of_sex_development (1 variants)
• Scoliosis,_isolated,_susceptibility_to,_3 (1 variants)
• Hypothyroidism (1 variants)
• Monogenic_hearing_loss (1 variants)
• Pulmonary_artery_atresia (1 variants)
• VATER_association (1 variants)
• Abnormal_facial_shape (1 variants)
• Iris_coloboma (1 variants)
• Male_infertility_with_spermatogenesis_disorder (1 variants)
• HYPOGONADOTROPIC_HYPOGONADISM_5_WITHOUT_ANOSMIA (1 variants)
• Wiedemann-Steiner_syndrome (1 variants)
• Atrial_septal_defect (1 variants)
• Familial_atrioventricular_septal_defect (1 variants)
• Myopia (1 variants)
• Pure_gonadal_dysgenesis_46,XY (1 variants)
• Chromatinopathy (1 variants)
• Premature_ovarian_failure (1 variants)
• CHD7_disorder (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• Pyloric_stenosis (1 variants)
• Chorioretinal_coloboma (1 variants)
• Joubert_syndrome (1 variants)
• Cleft_palate (1 variants)
• Congenital_heart_disease_(variable) (1 variants)
• Developmental_disorder (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. These statistics are base on transcript: NM_000017780.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	20	737	66	825
missense	27	84	1397	537	105	2150
nonsense	214	21	2			237
start loss						0
frameshift	316	68	3			387
splice donor/acceptor (+/-2bp)	56	39	7	2		104
Total	613	214	1429	1276	171

Highest pathogenic variant AF is 0.000025476282

GnomAD

Source: gnomAD

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
		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: dbNSFP

• 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

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

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