SLC25A36

Chr 3AR

solute carrier family 25 member 36

Also known as: HHF8, PNC2

NCBI Gene: 55186 ENSG00000114120 UniProt: Q96CQ1 OMIM: 616149

Enables pyrimidine nucleotide transmembrane transporter activity. Involved in pyrimidine nucleotide import into mitochondrion. Located in mitochondrion. Implicated in familial hyperinsulinemic hypoglycemia 8. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyperinsulinemic hypoglycemia, familial, 8MIM #620211

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hyperinsulinemic hypoglycemia, familial; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.034

Z-score 2.33

OE 0.34 (0.18–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.92Z-score

OE missense 0.57 (0.48–0.68)

91 obs / 159.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.18–0.72)

0≤0.351.4

Missense OE?0.57 (0.48–0.68)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 5 / 14.6Missense obs/exp: 91 / 159.2Syn Z: 0.15

Background carrier burden — how many people carry a rare variant somewhere in SLC25A36?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

318 rare PASS variants

Rare truncating (LoF)

1 in 5,500

57 rare PASS variants

Rare synonymous (reference)

1 in 140

151 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC25A36. 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 300	1 in 5,300
South Asian	~43k	1 in 230	1 in 5,000
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 27,000
European (Finnish)	~27k	1 in 780	1 in 2,800
Admixed American	~22k	1 in 290	1 in 2,800
African / African American	~21k	1 in 320	≈ 1 in 4,300
East Asian	~20k	1 in 220	≈ 1 in 15,000
Ashkenazi Jewish	~13k	1 in 2,400	≈ 1 in 3,700
Middle Eastern	~2,884	1 in 170	none seen

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): 3 of 7 coding exons well covered in gnomAD exomes; exons 1, 3, 4, 5 marginal. Genomes: 6 of 7 (exon 1 below).? see exons ↓