MTCL1

Chr 18

microtubule crosslinking factor 1

Also known as: CCDC165, KIAA0802, SOGA2

MTCL1 encodes a microtubule-associated protein that regulates microtubule dynamics in polarized epithelial cells and is required for faithful chromosome segregation during mitosis. Mutations cause autosomal recessive microcephaly, seizures, and developmental delay. This gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
107
P/LP submissions
0%
P/LP missense
0.45
LOEUF
Mechanism
Clinical SummaryMTCL1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
102 unique Pathogenic / Likely Pathogenic· 303 VUS of 477 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.000
Z-score 5.16
OE 0.31 (0.220.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.61Z-score
OE missense 1.05 (1.001.11)
1043 obs / 989.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.31 (0.220.45)
00.351.4
Missense OE1.05 (1.001.11)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 20 / 64.8Missense obs/exp: 1043 / 989.0Syn Z: -1.45

ClinVar Variant Classifications

477 submitted variants in ClinVar

Classification Summary

Pathogenic100
Likely Pathogenic2
VUS303
Likely Benign49
Benign7
Conflicting1
100
Pathogenic
2
Likely Pathogenic
303
VUS
49
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
100
0
100
Likely Pathogenic
0
0
2
0
2
VUS
0
292
11
0
303
Likely Benign
0
40
2
7
49
Benign
0
3
0
4
7
Conflicting
1
Total033511511462

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

View in ClinVar →

Protein Context — Lollipop Plot

MTCL1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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