FIRRM

Chr 1

FIGNL1 interacting regulator of recombination and mitosis

Also known as: Apolo1, C1orf112, FLIP, MEICA1

NCBI Gene: 55732 ENSG00000000460 UniProt: Q9NSG2 OMIM: 621430

FIRRM regulates PLK1 kinase activity at kinetochores and promotes faithful chromosome segregation during cell division, and in complex with FIGL1 regulates homologous recombination for DNA repair. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), but no human disease has been definitively associated with FIRRM mutations to date. Given its critical role in chromosome segregation and DNA repair, mutations would likely affect multiple organ systems if pathogenic variants are identified.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein kinase binding activity. Involved in several processes, including chromosome segregation; interstrand cross-link repair; and regulation of protein kinase activity. Located in several cellular components, including midbody; nuclear lumen; and spindle midzone. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.73

Clinical Summary— FIRRM

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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

49 VUS of 92 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 3.00

OE 0.52 (0.37–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.57Z-score

OE missense 0.92 (0.85–1.00)

396 obs / 429.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.37–0.73)

0≤0.351.4

Missense OE?0.92 (0.85–1.00)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 23 / 44.6Missense obs/exp: 396 / 429.4Syn Z: 0.89

ClinVar Variant Classifications

92 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign5

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	48	1	0	49
Likely Benign	5	0	0	5
Benign	2	0	1	3
Total	55	1	1	57

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap FIRRM — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →