HSD3B7

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 16:30985207-30989147

Links

ENSG00000099377 ∙ NCBI:80270 ∙ OMIM:607764 ∙ HGNC:18324 ∙ Uniprot:Q9H2F3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital bile acid synthesis defect 1 (Definitive), mode of inheritance: AR
• congenital bile acid synthesis defect 1 (Supportive), mode of inheritance: AR
• congenital bile acid synthesis defect 1 (Strong), mode of inheritance: AR
• congenital bile acid synthesis defect 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bile acid synthesis defect, congenital, 1	AR	Gastrointestinal	Due to early-onset progressive hepatic disease, affected invididuals commonly present in infancy with failure to thrive and coagulopathy, and typically demonstrate a favorable response to medical treatment (with oral bile acid therapy)	Gastrointestinal	3470305; 11067870; 12679481; 22095780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD3B7 gene.

• not provided (11 variants)
• Congenital bile acid synthesis defect 1 (5 variants)
• HSD3B7-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD3B7 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			5	23	3	31
missense	1		62	2	4	69
nonsense	2	1				3
start loss						0
frameshift	8	3				11
inframe indel						0
splice donor/acceptor (+/-2bp)	1	4				5
splice region			5	1	2	8
non coding				3	6	9
Total	12	8	67	28	13

Highest pathogenic variant AF is 0.0000131

Variants in HSD3B7

This is a list of pathogenic ClinVar variants found in the HSD3B7 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-30985474-C-T			Benign (Jul 09, 2018)
16-30985550-C-G			Benign (Jul 09, 2018)
16-30985551-G-C			Benign (Jul 09, 2018)
16-30985652-GC-TT			Uncertain significance (Jun 05, 2018)
16-30985664-C-A		HSD3B7-related disorder	Likely benign (Aug 16, 2022)
16-30985665-G-A			Conflicting classifications of pathogenicity (Jan 22, 2024)
16-30985698-G-T		Inborn genetic diseases • HSD3B7-related disorder	Uncertain significance (Aug 05, 2024)
16-30985702-CAG-C		Congenital bile acid synthesis defect 1 • HSD3B7-related disorder • Congenital bile acid synthesis defect	Pathogenic (Nov 11, 2024)
16-30985729-A-G		not specified	Benign (Dec 04, 2023)
16-30985730-C-G		Inborn genetic diseases	Uncertain significance (Sep 26, 2024)
16-30985730-C-T			Likely benign (Mar 31, 2023)
16-30985737-C-T		HSD3B7-related disorder	Pathogenic (Jun 27, 2024)
16-30985738-G-A		Inborn genetic diseases	Uncertain significance (Jun 12, 2023)
16-30985752-C-T			Uncertain significance (Sep 15, 2017)
16-30985761-C-G		not specified	Conflicting classifications of pathogenicity (May 01, 2024)
16-30985761-C-T		Inborn genetic diseases	Uncertain significance (Jul 08, 2024)
16-30985762-G-A		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
16-30985766-C-T		HSD3B7-related disorder	Likely benign (Aug 10, 2021)
16-30985787-C-G		Inborn genetic diseases	Uncertain significance (May 14, 2024)
16-30985793-C-G		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
16-30985801-C-G		Congenital bile acid synthesis defect 1	Uncertain significance (Nov 03, 2020)
16-30985825-G-A			Pathogenic (Aug 23, 2017)
16-30985831-G-T			Uncertain significance (Mar 22, 2016)
16-30986042-C-A		not specified	Benign (-)
16-30986042-C-T		not specified	Benign (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD3B7	protein_coding	protein_coding	ENST00000297679	6	3955

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.69e-8	0.298	125698	0	49	125747	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.768	202	235	0.859	0.0000166	2303
Missense in Polyphen		73	84.065	0.86837		858
Synonymous	1.10	91	105	0.864	0.00000754	810
Loss of Function	0.590	13	15.5	0.838	7.67e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000684	0.000663
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.0000548	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000239	0.000229
Middle Eastern	0.0000548	0.0000544
South Asian	0.000201	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. Does not metabolize several different C(19/21) steroids as substrates. Involved in bile acid synthesis (PubMed:11067870). Plays a key role in cell positioning and movement in lymphoid tissues by mediating degradation of 7-alpha,25-dihydroxycholesterol (7- alpha,25-OHC): 7-alpha,25-OHC acts as a ligand for the G protein- coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells. {ECO:0000250|UniProtKB:Q9EQC1, ECO:0000269|PubMed:11067870}.
• Disease: DISEASE: Congenital bile acid synthesis defect 1 (CBAS1) [MIM:607765]: A primary defect in bile synthesis leading to progressive liver disease. Clinical features include neonatal jaundice, severe intrahepatic cholestasis, cirrhosis. {ECO:0000269|PubMed:11067870, ECO:0000269|PubMed:12679481}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary bile acid biosynthesis - Homo sapiens (human);27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Metabolism of lipids;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids;bile acid biosynthesis, neutral pathway (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.167
• rvis_EVS: -0.2
• rvis_percentile_EVS: 39.11

Haploinsufficiency Scores

• pHI: 0.204
• hipred: N
• hipred_score: 0.170
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.748

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hsd3b7
• Phenotype: liver/biliary system 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); digestive/alimentary phenotype; growth/size/body region 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: bile acid biosynthetic process;cholesterol catabolic process;B cell chemotaxis;oxidation-reduction process
• Cellular component: cellular_component;endoplasmic reticulum membrane;lipid droplet;integral component of membrane
• Molecular function: 3-beta-hydroxy-delta5-steroid dehydrogenase activity;protein binding;oxidoreductase activity;oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor;cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity