HSD17B12

Chr 11

hydroxysteroid 17-beta dehydrogenase 12

Also known as: KAR, SDR12C1

NCBI Gene: 51144ENSG00000149084UniProt: Q53GQ0

This gene encodes a very important 17beta-hydroxysteroid dehydrogenase (17beta-HSD) that converts estrone into estradiol in ovarian tissue. This enzyme is also involved in fatty acid elongation. [provided by RefSeq, Oct 2011]

0
Active trials
15
Pathogenic / LP
68
ClinVar variants
21
Pubs (1 yr)
—
Missense Z
—
LOEUF
Clinical Summary— HSD17B12
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 51 VUS of 68 total submissions
📖
GeneReview available — HSD17B12
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

DNGOF
DN
0.85top 5%
GOF
0.7126th %ile
LOF
0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS51
Likely Benign2
13
Pathogenic
2
Likely Pathogenic
51
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
2
0
2
VUS
0
44
7
0
51
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total04622068

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

HSD17B12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
The Non-Coding Regulatory Variant rs2863002 at chr11p11.2 Increases Neuroblastoma Risk by Affecting HSD17B12 Expression and Lipid Metabolism.
Maiorino T et al.·Adv Sci (Weinh)
2025
An Integrative Phenotype-Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies HSD17B12 as a Candidate Gene for Obesity and Type 2 Diabetes.
Hachim MY et al.·Genes (Basel)
2020
Genetic variants in ELOVL2 and HSD17B12 predict melanoma-specific survival.
Dai W et al.·Int J Cancer
2019
Functional genetic variant of HSD17B12 in the fatty acid biosynthesis pathway predicts the outcome of colorectal cancer.
Lin Y et al.·J Cell Mol Med
2020Functional
Characterization of altered microRNAs related to different phenotypes of polycystic ovarian syndrome (PCOS) in serum, follicular fluid, and cumulus cells.
Motahari Rad H et al.·Taiwan J Obstet Gynecol
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients