MAIP1

Chr 2

matrix AAA peptidase interacting protein 1

Also known as: C2orf47

NCBI Gene: 79568ENSG00000162972UniProt: Q8WWC4OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.28
Clinical Summary— MAIP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 7 VUS of 49 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 OE0.76 (0.47–1.28)
0≤0.351.4
Missense OE0.85 (0.73–0.98)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 10 / 13.2Missense obs/exp: 131 / 154.8Syn Z: 0.11
DN
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

49 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS7
Likely Benign2
32
Pathogenic
1
Likely Pathogenic
7
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
0
5
2
0
7
Likely Benign
1
1
0
0
2
Benign
0
0
0
0
0
Total1635042

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

View in ClinVar →

Protein Context — Lollipop Plot

MAIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients