FANCM

Chr 14AR

FA complementation group M

Also known as: FAAP250, KIAA1596, POF15, SPGF28

NCBI Gene: 57697ENSG00000187790UniProt: Q8IYD8

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Primary Disease Associations & Inheritance

Premature ovarian failure 15MIM #618096
AR
Spermatogenic failure 28MIM #618086
AR
2
Active trials
0
Pathogenic / LP
0
ClinVar variants
46
Pubs (1 yr)
-0.1
Missense Z
0.59
LOEUF
Clinical Summary— FANCM
🧬
Gene-Disease Validity (ClinGen)
hereditary breast carcinoma · ADLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — FANCM
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 4.73
OE 0.46 (0.35–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.13Z-score
OE missense 1.01 (0.96–1.06)
1053 obs / 1041.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.46 (0.35–0.59)
0≤0.351.4
Missense OE1.01 (0.96–1.06)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 40 / 87.9Missense obs/exp: 1053 / 1041.0Syn Z: -0.00
DN
DN
0.6647th %ile
GOF
0.2497th %ile
LOF
0.3941th %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

0 submitted variants in ClinVar

ClinVar

FANCM · protein map & ClinVar variants

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

Gene2Phenotype Curations

FANCM-related Fanconi anemia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
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 5 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