The MAP7D2 protein stabilizes microtubules and serves as a critical cofactor for kinesin transport, regulating kinesin-1 recruitment to microtubules and contributing to axonal transport. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, presenting in infancy with seizures, severe developmental delay, and progressive microcephaly. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.478), consistent with its role in critical neuronal transport processes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.48
Clinical SummaryMAP7D2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
100 unique Pathogenic / Likely Pathogenic· 117 VUS of 300 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.041
Z-score 3.85
OE 0.27 (0.160.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.25Z-score
OE missense 1.04 (0.951.14)
306 obs / 294.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.27 (0.160.48)
00.351.4
Missense OE1.04 (0.951.14)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 9 / 32.8Missense obs/exp: 306 / 294.1Syn Z: -0.35
DN
0.73top 25%
GOF
0.5953th %ile
LOF
0.4430th %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

300 submitted variants in ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic6
VUS117
Likely Benign13
Benign1
Conflicting1
94
Pathogenic
6
Likely Pathogenic
117
VUS
13
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
94
0
94
Likely Pathogenic
0
0
6
0
6
VUS
0
105
12
0
117
Likely Benign
1
11
1
0
13
Benign
0
0
0
1
1
Conflicting
1
Total11161131232

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

View in ClinVar →

Protein Context — Lollipop Plot

MAP7D2 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC