MAIP1

Chr 2

matrix AAA peptidase interacting protein 1

Also known as: C2orf47

NCBI Gene: 79568 ENSG00000162972 UniProt: Q8WWC4 OMIM: 617267

The protein promotes mitochondrial calcium homeostasis by facilitating the maturation of SMDT1/EMRE, a component of the mitochondrial calcium uniporter complex. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene is highly intolerant to loss-of-function variants, reflecting its critical role in mitochondrial function.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable ribosome binding activity. Involved in calcium import into the mitochondrion; mitochondrial calcium ion homeostasis; and protein insertion into mitochondrial membrane. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.28

Clinical Summary— MAIP1

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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 VUS of 14 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?

1.28LOEUF

pLI 0.000

Z-score 0.82

OE 0.76 (0.47–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.68Z-score

OE missense 0.85 (0.73–0.98)

131 obs / 154.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.47–1.28)

0≤0.351.4

Missense OE?0.85 (0.73–0.98)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 10 / 13.2Missense obs/exp: 131 / 154.8Syn Z: 0.11

This gene — mechanism propensity

0.6161th %ile

GOF

0.5169th %ile

LOF

0.2970th %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

14 submitted variants in ClinVar

ClinVar

Classification Summary

VUS5

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	5	5
Likely Benign	1	1	2
Benign	0	0	0
Total	1	6	7

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap MAIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →