SLC25A33

Chr 1

solute carrier family 25 member 33

Also known as: BMSC-MCP, PNC1

NCBI Gene: 84275 ENSG00000171612 UniProt: Q9BSK2 OMIM: 610816

SLC25A33 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

OMIM Research

SLC25A33 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.82

Clinical Summary— SLC25A33

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

38 VUS of 57 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.006

Z-score 2.04

OE 0.42 (0.23–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.82 (0.72–0.94)

144 obs / 175.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.23–0.82)

0≤0.351.4

Missense OE?0.82 (0.72–0.94)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 6 / 14.4Missense obs/exp: 144 / 175.1Syn Z: -0.56

This gene — mechanism propensity

0.87top 5%

GOF

0.77top 25%

LOF

0.2287th %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

57 submitted variants in ClinVar

ClinVar

Classification Summary

VUS38

Likely Benign4

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	38	0	0	38
Likely Benign	0	1	3	4
Benign	0	0	2	2
Total	38	1	5	44

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap SLC25A33 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →