NSDHL
Basic information
Region (hg38): X:152830967-152869729
Links
Phenotypes
GenCC
Source:
- CHILD syndrome (Supportive), mode of inheritance: XL
- CK syndrome (Supportive), mode of inheritance: XL
- CHILD syndrome (Strong), mode of inheritance: XL
- CK syndrome (Strong), mode of inheritance: XL
- CK syndrome (Definitive), mode of inheritance: XL
- CHILD syndrome (Definitive), mode of inheritance: XL
- CK syndrome (Moderate), mode of inheritance: XL
- CHILD syndrome (Strong), mode of inheritance: XL
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome); CK syndrome | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Cardiovascular; Dermatologic; Musculoskeletal; Pulmonary; Renal | 5696317; 7408908; 8882402; 10710233; 10710235; 11907515; 12966526; 19842190; 19377476; 20605772; 21129721; 21290788 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (167 variants)
- Child_syndrome (52 variants)
- CK_syndrome (41 variants)
- Inborn_genetic_diseases (33 variants)
- not_specified (21 variants)
- NSDHL-related_disorder (17 variants)
- Connective_tissue_disorder (7 variants)
- Intellectual_disability (4 variants)
- Mitral_valve_prolapse (1 variants)
- Abnormal_cerebral_white_matter_morphology (1 variants)
- Arachnodactyly (1 variants)
- Tall_stature (1 variants)
- Hearing_impairment (1 variants)
- Delayed_speech_and_language_development (1 variants)
- Long_face (1 variants)
- Joint_hypermobility (1 variants)
- Scoliosis (1 variants)
- High_palate (1 variants)
- Seizure (1 variants)
- Frontoparietal_polymicrogyria (1 variants)
- Unilateral_polymicrogyria (1 variants)
- Dolichocephaly (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSDHL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015922.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 31 | 11 | 43 | |||
missense | 78 | 35 | 131 | |||
nonsense | 6 | |||||
start loss | 0 | |||||
frameshift | 5 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
Total | 11 | 10 | 80 | 66 | 20 |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
NSDHL | protein_coding | protein_coding | ENST00000370274 | 7 | 38763 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.964 | 0.0360 | 0 | 0 | 0 | 0 | 0.00 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.869 | 124 | 154 | 0.803 | 0.0000124 | 2453 |
Missense in Polyphen | 22 | 50.608 | 0.43471 | 827 | ||
Synonymous | -1.02 | 74 | 63.7 | 1.16 | 0.00000545 | 740 |
Loss of Function | 2.98 | 0 | 10.3 | 0.00 | 7.28e-7 | 179 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00 | 0.00 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00 | 0.00 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis. {ECO:0000269|PubMed:14506130}.;
- Disease
- DISEASE: CK syndrome (CKS) [MIM:300831]: A disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus. {ECO:0000269|PubMed:21129721}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Steroid biosynthesis - Homo sapiens (human);Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Cholesterol Biosynthesis;Metabolism of lipids;zymosterol biosynthesis;Glycine Serine metabolism;Squalene and cholesterol biosynthesis;Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;cholesterol biosynthesis I;Cholesterol biosynthesis
(Consensus)
Recessive Scores
- pRec
- 0.189
Intolerance Scores
- loftool
- rvis_EVS
- -0.2
- rvis_percentile_EVS
- 38.98
Haploinsufficiency Scores
- pHI
- 0.0804
- hipred
- Y
- hipred_score
- 0.582
- ghis
- 0.484
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.655
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nsdhl
- Phenotype
- skeleton 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; vision/eye 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); 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); pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- hair follicle development;cholesterol biosynthetic process;smoothened signaling pathway;cholesterol metabolic process;oxidation-reduction process;labyrinthine layer blood vessel development
- Cellular component
- endoplasmic reticulum;endoplasmic reticulum membrane;lipid droplet;integral component of membrane
- Molecular function
- C-3 sterol dehydrogenase (C-4 sterol decarboxylase) activity;3-beta-hydroxy-delta5-steroid dehydrogenase activity;oxidoreductase activity;oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor;sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) activity;4alpha-carboxy-4beta-methyl-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-oxidoreductase (decarboxylating) activity;4alpha-carboxy-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-dehydrogenase (decarboxylating) activity