NSDHL

NAD(P) dependent steroid dehydrogenase-like, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): X:152830967-152869729

Links

ENSG00000147383 ∙ NCBI:50814 ∙ OMIM:300275 ∙ HGNC:13398 ∙ Uniprot:Q15738 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CK syndrome (Moderate), mode of inheritance: XL
• CHILD syndrome (Strong), mode of inheritance: XL
• CHILD syndrome (Strong), mode of inheritance: XL
• CK syndrome (Strong), mode of inheritance: XL
• CHILD syndrome (Supportive), mode of inheritance: XL
• CK syndrome (Supportive), mode of inheritance: XL
• CK syndrome (Definitive), mode of inheritance: XL
• CHILD syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the NSDHL gene.

• not_provided (175 variants)
• Child_syndrome (52 variants)
• CK_syndrome (41 variants)
• Inborn_genetic_diseases (36 variants)
• not_specified (22 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			17	34	11	62
missense	2	7	114	36	8	167
nonsense	6		4			10
start loss						0
frameshift	3	2				5
splice donor/acceptor (+/-2bp)		1	16			17
Total	11	10	151	70	19

GnomAD

Source: gnomAD

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	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: dbNSFP

• 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

• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.98

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

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