TAMM41

Chr 3AR

TAM41 mitochondrial translocator assembly and maintenance homolog

Also known as: C3orf31, COXPD56, RAM41, TAM41

NCBI Gene: 132001 ENSG00000144559 UniProt: Q96BW9 OMIM: 614948

TAMM41 encodes a mitochondrial enzyme that catalyzes the conversion of phosphatidic acid to CDP-diacylglycerol, an essential step in cardiolipin biosynthesis. Mutations cause combined oxidative phosphorylation deficiency 56, a mitochondrial disorder affecting cellular energy production. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable phosphatidate cytidylyltransferase activity. Predicted to be involved in CDP-diacylglycerol biosynthetic process and cardiolipin biosynthetic process. Is active in mitochondrion. Implicated in combined oxidative phosphorylation deficiency 56. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.061 OMIM phenotype

Clinical Summary— TAMM41

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 49 VUS of 74 total submissions

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?

1.06LOEUF

pLI 0.000

Z-score 1.37

OE 0.65 (0.42–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.88–1.14)

172 obs / 171.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.42–1.06)

0≤0.351.4

Missense OE?1.00 (0.88–1.14)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 12 / 18.3Missense obs/exp: 172 / 171.8Syn Z: -1.03

This gene — mechanism propensity

0.6357th %ile

GOF

0.5857th %ile

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS49

Likely Benign6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	0	0	1	0	1
VUS	1	48	0	0	49
Likely Benign	0	2	0	4	6
Benign	0	0	0	0	0
Total	3	52	1	4	60

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap TAMM41 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →