NSDHL (NAD(P) dependent 3-beta-hydroxysteroid dehydrogenase NSDHL)

Gene

• Entrez ID: 50814
• Gene name: NAD(P) dependent 3-beta-hydroxysteroid dehydrogenase NSDHL
• Gene symbol: NSDHL
• Synonyms (NCBI Gene): H105E3, SDR31E1, XAP104
• Chromosome: X
• Chromosome location: Xq28
• Summary: The protein encoded by this gene is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis. Mutations in this gene are associated with CHILD syndrome, which is a X-linked dominant disorder of lipid metabolism with disturbed cho

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894901	G>A	Pathogenic	Coding sequence variant, missense variant
rs104894902	C>T	Pathogenic	Coding sequence variant, stop gained
rs104894903	C>T	Pathogenic	Coding sequence variant, stop gained
rs104894904	G>C	Pathogenic	Coding sequence variant, missense variant
rs104894905	G>T	Pathogenic	Coding sequence variant, stop gained
rs104894909	C>T	Pathogenic	Coding sequence variant, missense variant
rs121909833	GAA>-	Pathogenic	Coding sequence variant, inframe deletion
rs121909834	->T	Pathogenic	Coding sequence variant, frameshift variant
rs137853862	G>A	Pathogenic	Coding sequence variant, missense variant
rs137853863	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs141571609	C>A,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs375100066	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs587784222	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs587784223	C>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs587784224	G>A	Likely-pathogenic, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs587784225	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs587784226	C>A,T	Pathogenic	Synonymous variant, stop gained, coding sequence variant
rs797045835	->CATG	Pathogenic	Frameshift variant, coding sequence variant
rs1328593149	C>A,T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs1602937895	C>T	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016464	hsa-miR-193b-3p	Proteomics	21512034
MIRT1194887	hsa-miR-1252	CLIP-seq
MIRT1194888	hsa-miR-145	CLIP-seq
MIRT1194889	hsa-miR-3977	CLIP-seq
MIRT1194890	hsa-miR-4763-5p	CLIP-seq
MIRT1194891	hsa-miR-654-3p	CLIP-seq
MIRT1194892	hsa-miR-1265	CLIP-seq
MIRT1194893	hsa-miR-134	CLIP-seq
MIRT1194894	hsa-miR-3118	CLIP-seq
MIRT1194895	hsa-miR-4271	CLIP-seq
MIRT1194896	hsa-miR-4533	CLIP-seq
MIRT1194897	hsa-miR-4725-3p	CLIP-seq
MIRT1194898	hsa-miR-4747-5p	CLIP-seq
MIRT2056593	hsa-miR-298	CLIP-seq
MIRT2056594	hsa-miR-3135	CLIP-seq
MIRT2056595	hsa-miR-4438	CLIP-seq
MIRT2056596	hsa-miR-513a-5p	CLIP-seq
MIRT2285032	hsa-miR-24	CLIP-seq
MIRT2285033	hsa-miR-3155	CLIP-seq
MIRT2285034	hsa-miR-3155b	CLIP-seq
MIRT2056595	hsa-miR-4438	CLIP-seq
MIRT2285035	hsa-miR-484	CLIP-seq
MIRT2056596	hsa-miR-513a-5p	CLIP-seq
MIRT2582998	hsa-miR-1825	CLIP-seq
MIRT2582999	hsa-miR-199a-5p	CLIP-seq
MIRT2583000	hsa-miR-199b-5p	CLIP-seq
MIRT2583001	hsa-miR-3925-3p	CLIP-seq
MIRT2583002	hsa-miR-4663	CLIP-seq
MIRT2582998	hsa-miR-1825	CLIP-seq
MIRT2582999	hsa-miR-199a-5p	CLIP-seq
MIRT2583000	hsa-miR-199b-5p	CLIP-seq
MIRT2686628	hsa-miR-3657	CLIP-seq
MIRT2583001	hsa-miR-3925-3p	CLIP-seq
MIRT2583002	hsa-miR-4663	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000252	Function	3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity	IEA
GO:0000252	Function	3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity	TAS
GO:0001942	Process	Hair follicle development	IEA
GO:0003854	Function	3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity	TAS	10710235
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IC	10710235
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005811	Component	Lipid droplet	IDA	14741744, 21498505
GO:0005811	Component	Lipid droplet	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006694	Process	Steroid biosynthetic process	IEA
GO:0006695	Process	Cholesterol biosynthetic process	IC	10710235
GO:0006695	Process	Cholesterol biosynthetic process	IEA
GO:0006695	Process	Cholesterol biosynthetic process	TAS	10710235
GO:0007224	Process	Smoothened signaling pathway	IEA
GO:0008202	Process	Steroid metabolic process	IEA
GO:0008203	Process	Cholesterol metabolic process	IBA
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0016020	Component	Membrane	IEA
GO:0016126	Process	Sterol biosynthetic process	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016616	Function	Oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IBA
GO:0016616	Function	Oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA
GO:0060716	Process	Labyrinthine layer blood vessel development	IEA
GO:0102175	Function	3-beta-hydroxysteroid dehydrogenase (NAD+)/C4-decarboxylase activity	IEA

Other IDs

• MIM: 300275
• HGNC: 13398
• e!Ensembl: ENSG00000147383

Protein

• UniProt ID: Q15738
• Protein name: Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (EC 1.1.1.170) (Protein H105e3)
• Protein function: Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis (By similarity). Also plays a role in the regulation of the endocytic trafficking of EGFR (By
• PDB: 6JKG, 6JKH
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01073	3Beta_HSD	41 → 297	3-beta hydroxysteroid dehydrogenase/isomerase family	Family

• Tissue specificity: TISSUE SPECIFICITY: Brain, heart, liver, lung, kidney, skin and placenta.
• Sequence:

  MEPAVSEPMRDQVARTHLTEDTPKVNADIEKVNQNQAKRCTVIGGSGFLGQHMVEQLLAR
  GYAVNVFDIQQGFDNPQVRFFLGDLCSRQDLYPALKGVNTVFHCASPPPSSNNKELFYRV
  NYIGTKNVIETCKEAGVQKLILTSSASVIFEGVDIKNGTEDLPYAMKPIDYYTETKILQE
  RAVLGANDPEKNFLTTAIRPHGIFGPRDPQLVPILIEAARNGKMKFVIGNGKNLVDFTFV
  ENVVHGHILAAEQLSRDSTLGGKAFHITNDEPIPFWTFLSRILTGLNYEAPKYHIPYWVA
  YYLALLLSLLVMVISPVIQLQPTFTPMRVALAGTFHYYSCERAKKAMGYQPLVTMDDAME
  RTVQSFRHLRRVK

• Sequence length: 373

Pathways

KEGG:

Steroid biosynthesis
Metabolic pathways

Reactome:

Cholesterol biosynthesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Child syndrome	Pathogenic; Likely pathogenic	rs141571609, rs587784225, rs587784226, rs587784222, rs797045835, rs2521790020, rs104894909, rs104894901, rs104894902, rs104894903, rs104894904, rs104894905, rs137853863, rs1602937895	RCV000146965 RCV000146967 RCV000146968 RCV000146960 RCV000192617 RCV003148086 RCV000012179 RCV000012180 RCV000012181 RCV000012182 RCV000012183 RCV000012184 RCV000020427 RCV000985094	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
CK syndrome	Likely pathogenic; Pathogenic	rs2521790020, rs121909834, rs121909833	RCV003148087 RCV000020428 RCV000020430	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Malignant tumor of urinary bladder	Likely pathogenic	rs2125008883	RCV005912593	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thyroid cancer, nonmedullary, 1	Pathogenic	rs104894905	RCV005887447	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Abnormal cerebral white matter morphology	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARACHNODACTYLY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BYZANTHINE ARCH PALATE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONNECTIVE TISSUE DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Connective tissue disorder	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontoparietal polymicrogyria	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEARING IMPAIRMENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITRAL VALVE PROLAPSE SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NSDHL-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERISYLVIAN POLYMICROGYRIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS, UNSPECIFIED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seizure	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA OF HEAD AND NECK	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Unilateral polymicrogyria	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	30376821	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	18825599	Associate	★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	34513998	Associate	★☆☆☆☆ Found in Text Mining only
CHILD syndrome	Child Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Chondrodysplasia punctata, X-linked dominant type	Chondrodysplasia Punctata	BEFREE	31034146		★☆☆☆☆ Found in Text Mining only
CK syndrome	CK Syndrome	GENOMICS_ENGLAND_DG	10710235, 25900314, 27604308		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CK syndrome	CK Syndrome	CLINGEN_DG	19377476, 19842190, 21129721, 25900314		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CK syndrome	CK Syndrome	BEFREE	21129721, 25900314		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CK syndrome	CK Syndrome	ORPHANET_DG	21129721		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CK syndrome	CK Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CK syndrome	CK Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CK syndrome	CK Syndrome	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Common ventricle	Complete Atrioventricular Canal Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of kidneys syndrome	Renal agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital Hemidysplasia With Ichthyosiform Erythroderma And Limb Defects	BEFREE	10710235, 12966526, 16230564, 19906044, 22113624, 25093865, 29341259, 31034146		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital Hemidysplasia With Ichthyosiform Erythroderma And Limb Defects	GENOMICS_ENGLAND_DG	10710235, 27604308		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital Hemidysplasia With Ichthyosiform Erythroderma And Limb Defects	ORPHANET_DG	10710235, 11907515		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital Hemidysplasia With Ichthyosiform Erythroderma And Limb Defects	UNIPROT_DG	10710235, 11907515		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital hemidysplasia with ichthyosiform erythroderma and limb defects	Pubtator	18825599, 30376821, 33139364, 34957706, 35853659, 40222685	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital Hemidysplasia With Ichthyosiform Erythroderma And Limb Defects	CTD_human_DG	25526675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects	Congenital Hemidysplasia With Ichthyosiform Erythroderma And Limb Defects	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysphasia	Dysphasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gastrointestinal Diseases	Gastrointestinal disease	Pubtator	34957706	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Goldenhar Syndrome	Goldenhar syndrome	Pubtator	18825599	Associate	★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydronephrosis	Hydronephrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperkeratosis	Hyperkeratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma, Congenital	Ichthyosis Congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	21129721		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Intellectual developmental disorder	Pubtator	30376821	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Mental retardation	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanocytic nevus	Melanocytic nevus	BEFREE	10710235		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	35905688	Associate	★☆☆☆☆ Found in Text Mining only
Nevus	Nevus	BEFREE	10710235		★☆☆☆☆ Found in Text Mining only
NEVUS, EPIDERMAL (disorder)	Epidermal nevus	BEFREE	31571289		★☆☆☆☆ Found in Text Mining only
Pachygyria	Pachygyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Parakeratosis	Parakeratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Posteriorly rotated ear	Posteriorly Rotated Ear	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Single Ventricle Defect	Single Ventricle Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skin Diseases	Skin disease	Pubtator	34957706	Associate	★☆☆☆☆ Found in Text Mining only
Skin lesion	Skin Lesion	BEFREE	26459993, 31571289		★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	CTD_human_DG	23125191		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	33219617	Stimulate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only