DHRS12

Chr 13

dehydrogenase/reductase 12

Also known as: SDR40C1

NCBI Gene: 79758 ENSG00000102796 UniProt: A0PJE2

This gene encodes a short-chain dehydrogenase/reductase that functions as an oxidoreductase involved in metabolizing various compounds including steroid hormones, prostaglandins, retinoids, and lipids. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy. The gene shows no constraint against loss-of-function variants in population databases.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members in this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.28

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.28LOEUF

pLI 0.000

Z-score 0.71

OE 0.82 (0.54–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.95 (0.83–1.08)

170 obs / 179.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.54–1.28)

0≤0.351.4

Missense OE?0.95 (0.83–1.08)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 14 / 17.2Missense obs/exp: 170 / 179.5Syn Z: 0.89

Background carrier burden — how many people carry a rare variant somewhere in DHRS12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

493 rare PASS variants

Rare truncating (LoF)

1 in 860

114 rare PASS variants

Rare synonymous (reference)

1 in 300

209 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DHRS12. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 970
South Asian	~43k	1 in 98	1 in 660
Remaining (unassigned)	~30k	1 in 80	1 in 540
European (Finnish)	~27k	1 in 270	1 in 4,200
Admixed American	~22k	1 in 100	1 in 420
African / African American	~21k	1 in 76	1 in 400
East Asian	~20k	1 in 110	1 in 1,400
Ashkenazi Jewish	~13k	1 in 370	none seen
Middle Eastern	~2,884	1 in 88	≈ 1 in 670

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 8.? see exons ↓