HSD3B7

Summary

HSD3B7 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7, HGNC:18324) is a protein-coding gene on chromosome 16p11.2, encoding 3 beta-hydroxysteroid dehydrogenase type 7 (Q9H2F3). The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.

This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80270 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital bile acid synthesis defect 1 (Definitive, ClinGen)
• Clinical variants (ClinVar): 215 total — 17 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 30
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_025193

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18324
Approved symbol	HSD3B7
Name	hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	C(27)-3BETA-HSD, SDR11E3
Ensembl gene	ENSG00000099377
Ensembl biotype	protein_coding
OMIM	607764
Entrez	80270

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 25 protein_coding

ENST00000262520, ENST00000297679, ENST00000562932, ENST00000574447, ENST00000867900, ENST00000867901, ENST00000867902, ENST00000867903, ENST00000867904, ENST00000867905, ENST00000867906, ENST00000867907, ENST00000867908, ENST00000867909, ENST00000867910, ENST00000867911, ENST00000867912, ENST00000867913, ENST00000867914, ENST00000867915, ENST00000930187, ENST00000949918, ENST00000949919, ENST00000949920, ENST00000949921

RefSeq mRNA: 3 — MANE Select: NM_025193 NM_001142777, NM_001142778, NM_025193

CCDS: CCDS10698, CCDS45466

Canonical transcript exons

ENST00000297679 — 7 exons

Exon	Start	End
ENSE00000648509	30986423	30986531
ENSE00000648510	30986049	30986204
ENSE00000869445	30986605	30986704
ENSE00001236006	30986840	30987002
ENSE00001402950	30985653	30985824
ENSE00002630358	30985207	30985297
ENSE00003557461	30987768	30989147

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 95.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1903 / max 116.5271, expressed in 1509 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153753	7.0604	1473
153754	1.1862	560
153755	0.9199	403
153752	0.0239	9

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.67	gold quality
liver	UBERON:0002107	90.69	gold quality
left adrenal gland	UBERON:0001234	87.93	gold quality
left adrenal gland cortex	UBERON:0035825	87.71	gold quality
right adrenal gland	UBERON:0001233	87.49	gold quality
apex of heart	UBERON:0002098	86.15	gold quality
right adrenal gland cortex	UBERON:0035827	85.92	gold quality
adrenal cortex	UBERON:0001235	85.70	gold quality
mucosa of transverse colon	UBERON:0004991	85.53	gold quality
body of pancreas	UBERON:0001150	85.21	gold quality
metanephros cortex	UBERON:0010533	84.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.75	gold quality
adrenal gland	UBERON:0002369	83.41	gold quality
adult mammalian kidney	UBERON:0000082	83.25	gold quality
omental fat pad	UBERON:0010414	83.25	gold quality
skin of leg	UBERON:0001511	83.22	gold quality
peritoneum	UBERON:0002358	83.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.72	gold quality
transverse colon	UBERON:0001157	82.52	gold quality
small intestine	UBERON:0002108	82.24	gold quality
skin of abdomen	UBERON:0001416	82.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.95	gold quality
lower esophagus	UBERON:0013473	81.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.68	gold quality
mucosa of stomach	UBERON:0001199	81.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.49	gold quality
stromal cell of endometrium	CL:0002255	81.45	gold quality
synovial joint	UBERON:0002217	81.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting HSD3B7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-135A-2-3P	98.40	66.74	442
HSA-MIR-135B-3P	98.40	67.35	426

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 6)

• Mutations in the HSD3B7 gene account for autosomal recessive neonatal cholestasis caused by 3[beta]-hydroxy-[DELTA]5-C27-steroid dehydrogenase/isomerase deficiency. (PMID:20531254)
• Homozygosity mapping identifies a bile acid biosynthetic defect (3beta-HSD deficiency due to a frameshift mutation in HSD3B7) in an adult with cirrhosis of unknown etiology. (PMID:22095780)
• Expression of steroid sulfated transporters and 3beta-HSD activity in endometrium of polycystic ovary syndrome (PMID:26450365)
• Novel Mutations in the 3beta-hydroxy-5-C27-steroid Dehydrogenase Gene (HSD3B7) in a Patient with Neonatal Cholestasis. (PMID:26712441)
• In the classical pathway, HSD3B7 catalyzes the second step of bile acid formation and its mutations may reduce the synthetic capability. (PMID:29670816)
• Genetic spectrum and clinical characteristics of 3beta-hydroxy-Delta(5)-C27-steroid oxidoreductase (HSD3B7) deficiency in China. (PMID:34627351)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd3b7	ENSDARG00000036966
mus_musculus	Hsd3b7	ENSMUSG00000042289
rattus_norvegicus	Hsd3b7	ENSRNOG00000019080
caenorhabditis_elegans		WBGENE00022498
caenorhabditis_elegans		WBGENE00022616

Paralogs (10): TGDS (ENSG00000088451), GFUS (ENSG00000104522), GMDS (ENSG00000112699), UXS1 (ENSG00000115652), GALE (ENSG00000117308), NSDHL (ENSG00000147383), SDR42E2 (ENSG00000183921), SDR42E1 (ENSG00000184860), HSD3B1 (ENSG00000203857), HSD3B2 (ENSG00000203859)

Protein

Protein identifiers

3 beta-hydroxysteroid dehydrogenase type 7 — Q9H2F3 (reviewed: Q9H2F3)

Alternative names: 3 beta-hydroxysteroid dehydrogenase type VII, 3-beta-hydroxy-Delta(5)-C27 steroid oxidoreductase, Cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase

All UniProt accessions (3): Q9H2F3, I3L2H6, I3L2Q9

UniProt curated annotations — full annotation on UniProt →

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. 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.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; steroid biosynthesis.

Similarity. Belongs to the 3-beta-HSD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H2F3-1	1	yes
Q9H2F3-2	2

RefSeq proteins (3): NP_001136249, NP_001136250, NP_079469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002225	3Beta_OHSteriod_DH/Estase	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR050425	NAD(P)_dehydrat-like	Family

Pfam: PF01073

Catalyzed reactions (Rhea), 4 shown:

• 7alpha-hydroxycholesterol + NAD(+) = 7alpha-hydroxycholest-4-en-3-one + NADH + H(+) (RHEA:11896)
• 7alpha,25-dihydroxycholesterol + NAD(+) = 7alpha,25-dihydroxy-4-cholesten-3-one + NADH + H(+) (RHEA:47156)
• (25R)-cholest-5-en-3beta,7alpha,26-triol + NAD(+) = (25R)-7alpha,26-dihydroxycholest-4-en-3-one + NADH + H(+) (RHEA:47180)
• (24S)-7alpha-dihydroxycholesterol + NAD(+) = (24S)-7alpha,24-dihydroxycholest-4-en-3-one + NADH + H(+) (RHEA:47200)

UniProt features (12 total): sequence variant 4, transmembrane region 2, sequence conflict 2, chain 1, active site 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2F3-F1	94.01	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 159 (proton acceptor)

Ligand- & substrate-binding residues (1): 163

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193775	Synthesis of bile acids and bile salts via 24-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1430728	Metabolism
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-194068	Bile acid and bile salt metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 253 (showing top): AP1_01, GOBP_CELL_CHEMOTAXIS, GCANCTGNY_MYOD_Q6, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GGAMTNNNNNTCCY_UNKNOWN, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LEUKOCYTE_CHEMOTAXIS, NFKB_Q6, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (4): steroid biosynthetic process (GO:0006694), bile acid biosynthetic process (GO:0006699), B cell chemotaxis (GO:0035754), lipid metabolic process (GO:0006629)

GO Molecular Function (5): 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity (GO:0003854), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity (GO:0047016), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Synthesis of bile acids and bile salts	3
Bile acid and bile salt metabolism	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	1
lipid biosynthetic process	1
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
lymphocyte chemotaxis	1
primary metabolic process	1
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
oxidoreductase activity, acting on CH-OH group of donors	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
binding	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2759 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD3B7	AKR1D1	P51857	956
HSD3B7	AMACR	Q9UHK6	879
HSD3B7	CYP7B1	O75881	810
HSD3B7	CH25H	O95992	732
HSD3B7	CYP27A1	Q02318	678
HSD3B7	CYP8B1	Q9UNU6	656
HSD3B7	CYP7A1	P22680	643
HSD3B7	CYP39A1	Q9NYL5	636
HSD3B7	BAAT	Q14032	618
HSD3B7	CYP46A1	Q9Y6A2	579
HSD3B7	GPR183	P32249	571
HSD3B7	ACOX2	Q99424	571
HSD3B7	AKR1C4	P17516	565
HSD3B7	HSD17B4	P51659	544
HSD3B7	SLC27A5	Q9Y2P5	540

IntAct

177 interactions, top by confidence:

A	B	Type	Score
HSD3B7	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	HSD3B7	psi-mi:“MI:0915”(physical association)	0.720
HSD3B7		psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	SPRY2	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	HSD3B7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-2	HSD3B7	psi-mi:“MI:0915”(physical association)	0.560
	HSD3B7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	HSD3B7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	HSD3B7	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	TMX2	psi-mi:“MI:0915”(physical association)	0.560
HSD3B7	MEI4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (391): HSD3B7 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), HSD3B7 (Affinity Capture-RNA), HSD3B7 (Synthetic Lethality), HSD3B7 (Two-hybrid), HSD3B7 (Two-hybrid), HSD3B7 (Two-hybrid), HSD3B7 (Two-hybrid), HSD3B7 (Two-hybrid)

ESM2 similar proteins: A0A0H3KNE7, A0A3Q8GL18, A0A3Q8GLE8, A0A3Q8GYY4, A0A7N9VSG0, A0A7T8F1N2, A0A8F5XX49, A0A8I6GJ95, A0AAT9JA24, A5W4G5, A8C7R7, B8A5W4, D4A2B7, E9Q3D4, E9QUT3, G4N290, O35048, P0C622, P14061, P23102, P37440, P51656, P51661, P9WES5, P9WGQ2, P9WGQ3, Q08632, Q13268, Q17QU7, Q17QW3, Q4WR19, Q5C9I9, Q5R9W5, Q5SS80, Q7FAE1, Q7ZY31, Q8SPU8, Q8VBZ0, Q8XBJ4, Q91WL8

Diamond homologs: A0A059TC02, A0A072VDF2, A0A0B6VQ48, A8EZA9, A8GN21, A8GRN9, D7U6G6, G3XMB9, G7IYC1, G7JEE5, I3PLR3, O22133, O46516, O49163, P0DX24, P14720, P14721, P27364, P48279, P51102, P51103, P51104, P51105, P51106, P51107, P51108, P51109, P51110, P53111, P53183, P55584, P65685, P73212, P83775, P9WIH4, P9WIH5, P9WN66, P9WN67, P9WQP6, P9WQP7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	12	17.6×	2e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

215 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	9
Uncertain significance	109
Likely benign	46
Benign	16

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1385027	NM_025193.4(HSD3B7):c.721_722insAG (p.Ala241fs)	Pathogenic
1458547	NC_000016.9:g.(?30996980)(31021717_?)del	Pathogenic
191290	NM_025193.4(HSD3B7):c.694+2del	Pathogenic
2030273	NM_025193.4(HSD3B7):c.611del (p.Asp204fs)	Pathogenic
2697513	NM_025193.4(HSD3B7):c.618C>G (p.Tyr206Ter)	Pathogenic
286890	NM_025193.4(HSD3B7):c.890del (p.Phe297fs)	Pathogenic
2881	NM_025193.4(HSD3B7):c.1039_1040del (p.Leu347fs)	Pathogenic
2882	NM_025193.4(HSD3B7):c.294dup (p.Lys99fs)	Pathogenic
2884	NM_025193.4(HSD3B7):c.439G>A (p.Glu147Lys)	Pathogenic
2885	NM_025193.4(HSD3B7):c.45_46del (p.Gly17fs)	Pathogenic
3660663	NM_025193.4(HSD3B7):c.323-1G>C	Pathogenic
4291805	NM_025193.4(HSD3B7):c.16C>T (p.Gln6Ter)	Pathogenic
4710259	NM_025193.4(HSD3B7):c.503G>A (p.Trp168Ter)	Pathogenic
498040	NM_025193.4(HSD3B7):c.196del (p.Asp66fs)	Pathogenic
593800	NM_025193.4(HSD3B7):c.166+1G>A	Pathogenic
593957	NM_025193.4(HSD3B7):c.453del (p.Pro150_Tyr151insTer)	Pathogenic
593981	NM_025193.4(HSD3B7):c.268_281del (p.Val90fs)	Pathogenic
1977130	NM_025193.4(HSD3B7):c.531+1G>A	Likely pathogenic
2585402	NM_025193.4(HSD3B7):c.205C>T (p.Gln69Ter)	Likely pathogenic
2628801	NM_025193.4(HSD3B7):c.1025del (p.Phe342fs)	Likely pathogenic
2671755	NM_025193.4(HSD3B7):c.431+2T>C	Likely pathogenic
2761603	NM_025193.4(HSD3B7):c.532-2A>G	Likely pathogenic
2883	NM_025193.4(HSD3B7):c.322+1G>T	Likely pathogenic
3045782	NM_025193.4(HSD3B7):c.788_810del (p.Ser263fs)	Likely pathogenic
3580268	NM_025193.4(HSD3B7):c.323-1G>A	Likely pathogenic
3580269	NM_025193.4(HSD3B7):c.551del (p.Leu184fs)	Likely pathogenic

SpliceAI

1423 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30986417:T:TA	acceptor_gain	1.0000
16:30986491:G:GT	donor_gain	1.0000
16:30986530:AGGTG:A	donor_loss	1.0000
16:30986532:G:GC	donor_loss	1.0000
16:30986533:T:A	donor_loss	1.0000
16:30986600:A:AG	acceptor_gain	1.0000
16:30986600:ACCAG:A	acceptor_gain	1.0000
16:30986601:CCA:C	acceptor_loss	1.0000
16:30986602:CA:C	acceptor_loss	1.0000
16:30986603:A:AG	acceptor_gain	1.0000
16:30986603:A:G	acceptor_loss	1.0000
16:30986603:AG:A	acceptor_gain	1.0000
16:30986603:AGG:A	acceptor_gain	1.0000
16:30986603:AGGG:A	acceptor_gain	1.0000
16:30986604:G:GA	acceptor_gain	1.0000
16:30986604:G:GC	acceptor_loss	1.0000
16:30986604:GG:G	acceptor_gain	1.0000
16:30986604:GGG:G	acceptor_gain	1.0000
16:30986604:GGGG:G	acceptor_gain	1.0000
16:30986604:GGGGC:G	acceptor_gain	1.0000
16:30986701:G:GT	donor_gain	1.0000
16:30986702:A:T	donor_gain	1.0000
16:30986702:AAGG:A	donor_loss	1.0000
16:30986705:G:T	donor_loss	1.0000
16:30986706:T:A	donor_loss	1.0000
16:30986883:C:CA	acceptor_gain	1.0000
16:30986884:G:A	acceptor_gain	1.0000
16:30986946:G:GT	donor_gain	1.0000
16:30986946:G:T	donor_gain	1.0000
16:30986992:GGTC:G	donor_gain	1.0000

AlphaMissense

2345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30986482:A:C	S128R	0.996
16:30986484:C:A	S128R	0.996
16:30986484:C:G	S128R	0.996
16:30986485:A:C	S129R	0.995
16:30986487:C:A	S129R	0.995
16:30986487:C:G	S129R	0.995
16:30986662:G:C	K163N	0.995
16:30986662:G:T	K163N	0.995
16:30985716:T:C	F20L	0.994
16:30985718:C:A	F20L	0.994
16:30985718:C:G	F20L	0.994
16:30986486:G:T	S129I	0.994
16:30987772:T:A	N233K	0.994
16:30987772:T:G	N233K	0.994
16:30987850:C:G	C259W	0.994
16:30988064:T:C	F331L	0.994
16:30988066:C:A	F331L	0.994
16:30988066:C:G	F331L	0.994
16:30986483:G:T	S128I	0.993
16:30986876:C:A	R190S	0.992
16:30986895:G:T	G196V	0.992
16:30986197:C:A	N105K	0.990
16:30986197:C:G	N105K	0.990
16:30986657:A:C	S162R	0.990
16:30986659:C:A	S162R	0.990
16:30986659:C:G	S162R	0.990
16:30986648:T:C	Y159H	0.988
16:30987849:G:A	C259Y	0.988
16:30986895:G:A	G196D	0.987
16:30987771:A:T	N233I	0.987

dbSNP variants (sampled 300 via entrez): RS1000439099 (16:30985510 G>A,T), RS1001672044 (16:30986320 G>A,C,T), RS1002638811 (16:30987472 A>G), RS1002672275 (16:30985225 G>A,C), RS1002688076 (16:30987737 G>A,T), RS1003696640 (16:30989030 A>G,T), RS1003910220 (16:30988050 T>C), RS1004202672 (16:30983264 G>A), RS1004716531 (16:30986787 C>T), RS1005019672 (16:30984243 G>A), RS1005399367 (16:30984385 G>A,T), RS1005972113 (16:30985004 C>A,T), RS1006025956 (16:30985181 T>TGGGGCAGGGGCA), RS1006456162 (16:30985289 C>G,T), RS1007018409 (16:30983244 G>A)

Disease associations

OMIM: gene MIM:607764 | disease phenotypes: MIM:607765, MIM:616172, MIM:231100

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital bile acid synthesis defect 1	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital bile acid synthesis defect 1	Definitive	AR

Mondo (4): congenital bile acid synthesis defect 1 (MONDO:0011906), generalized epilepsy with febrile seizures plus, type 9 (MONDO:0014517), neonatal hemochromatosis (MONDO:0009275), congenital bile acid synthesis defect (MONDO:0018841)

Orphanet (4): Congenital bile acid synthesis defect type 1 (Orphanet:79301), Genetic epilepsy with febrile seizure plus (Orphanet:36387), Neonatal hemochromatosis (Orphanet:446), Congenital bile acid synthesis defect (Orphanet:485631)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000662	Nyctalopia
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000989	Pruritus
HP:0001080	Biliary tract abnormality
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001406	Intrahepatic cholestasis
HP:0001508	Failure to thrive
HP:0001744	Splenomegaly
HP:0001892	Abnormal bleeding
HP:0001928	Abnormality of coagulation
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002570	Steatorrhea
HP:0002630	Fat malabsorption
HP:0002748	Rickets
HP:0002908	Conjugated hyperbilirubinemia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003146	Hypocholesterolemia
HP:0003256	Abnormality of the coagulation cascade
HP:0003623	Neonatal onset
HP:0006566	Neonatal cholestatic liver disease
HP:0009830	Peripheral neuropathy
HP:0011985	Acholic stools
HP:0200084	Giant cell hepatitis
HP:6000825	Reduced C27 3beta-HSD activity in cultured fibroblasts

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535442	Bile acid synthesis defect, congenital, 1 (supp.)
C536394	Neonatal hemochromatosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Acetaminophen	decreases expression, affects cotreatment	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
Cyclosporine	decreases expression, affects cotreatment	3
bisphenol A	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
fipronil	increases expression	1
K 7174	decreases expression	1
obeticholic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1TY	Abcam HeLa HSD3B7 KO	Cancer cell line	Female

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns