MICALL1

Chr 22

MICAL like 1

Also known as: MICAL-L1, MIRAB13

NCBI Gene: 85377 ENSG00000100139 UniProt: Q8N3F8 OMIM: 619563

MICALL1 encodes a lipid-binding protein that regulates endosome membrane tubulation and slow endocytic recycling, and plays a role in ciliogenesis by recruiting proteins to the primary cilium. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene shows low constraint to loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including identical protein binding activity; phosphatidic acid binding activity; and small GTPase binding activity. Involved in several processes, including plasma membrane tubulation; protein localization to organelle; and slow endocytic recycling. Located in centriole; cilium; and endosome. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.75

Clinical Summary— MICALL1

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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

157 VUS of 182 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?

0.75LOEUF

pLI 0.000

Z-score 2.69

OE 0.50 (0.34–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.98Z-score

OE missense 0.88 (0.81–0.95)

444 obs / 505.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.34–0.75)

0≤0.351.4

Missense OE?0.88 (0.81–0.95)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 17 / 33.9Missense obs/exp: 444 / 505.8Syn Z: 0.94

This gene — mechanism propensity

0.6649th %ile

GOF

0.6442th %ile

LOF

0.3744th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

182 submitted variants in ClinVar

ClinVar

Classification Summary

VUS157

Likely Benign8

157

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	157	0	157
Likely Benign	6	2	8
Benign	0	0	0
Total	163	2	165

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap MICALL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →