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

• 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
• CK syndrome (Definitive), mode of inheritance: XLR
• CHILD syndrome (Definitive), mode of inheritance: XLD
• CHILD syndrome (Strong), 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.

• Child syndrome (4 variants)
• not provided (1 variants)
• CK syndrome (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.

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				23	11	34
missense		4	52	20	7	83
nonsense	3					3
start loss						0
frameshift	3	2				5
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			4	4		8
non coding			2	16	11	29
Total	6	7	55	59	29

Variants in NSDHL

This is a list of pathogenic ClinVar variants found in the NSDHL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-152831633-G-T			Uncertain significance (Nov 13, 2019)
X-152846040-C-T			Benign (Aug 31, 2018)
X-152846241-C-G			Likely benign (Jul 03, 2019)
X-152846330-A-G		NSDHL-related disorder	Likely benign (Feb 04, 2023)
X-152846340-A-T			Uncertain significance (Oct 18, 2023)
X-152846341-G-A			Uncertain significance (Nov 18, 2023)
X-152846342-C-G			Uncertain significance (Jun 08, 2022)
X-152846343-G-A		Inborn genetic diseases	Likely benign (Apr 19, 2024)
X-152846349-A-G		not specified	Benign/Likely benign (Jan 29, 2024)
X-152846354-A-G			Likely benign (Feb 08, 2022)
X-152846364-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 11, 2023)
X-152846366-A-G			Benign (Aug 09, 2022)
X-152846367-C-T		CK syndrome;Child syndrome	Uncertain significance (Apr 29, 2022)
X-152846368-G-A		CK syndrome	Conflicting classifications of pathogenicity (Jan 24, 2023)
X-152846389-C-T		Connective tissue disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 01, 2024)
X-152846394-A-G			Uncertain significance (Dec 02, 2022)
X-152846395-A-G			Conflicting classifications of pathogenicity (Aug 01, 2022)
X-152846407-A-G		NSDHL-related disorder	Benign (Oct 21, 2022)
X-152846451-C-T			Benign (Mar 12, 2023)
X-152846687-G-C			Likely benign (Aug 15, 2020)
X-152850003-A-G			Benign (Aug 31, 2018)
X-152850236-T-G			Likely benign (Dec 24, 2018)
X-152850247-G-A			Likely benign (Nov 24, 2022)
X-152850250-C-G			Likely benign (Apr 11, 2022)
X-152850260-CA-C			Likely benign (Jan 03, 2019)

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
0.964	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: 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

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