GeneBe

FANCM

FA complementation group M, the group of FA core complex|FA complementation groups|RNA helicases

Basic information

Region (hg38): 14:45135930-45200890

Previous symbols: [ "KIAA1596" ]

Links

ENSG00000187790 ∙ NCBI:57697 ∙ OMIM:609644 ∙ HGNC:23168 ∙ Uniprot:Q8IYD8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • spermatogenic failure 28 (Strong), mode of inheritance: AR
  • Fanconi anemia (Supportive), mode of inheritance: AR
  • male infertility with azoospermia or oligozoospermia due to single gene mutation (Supportive), mode of inheritance: AD
  • breast cancer (Disputed Evidence), mode of inheritance: AD
  • spermatogenic failure 28 (Strong), mode of inheritance: AR
  • Fanconi anemia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Premature ovarian failure 15ARObstetricIn Premature ovarian failure, genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiencyEndocrine; Genitourinary; Obstetric16116422; 20301575; 28837162
Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FANCM gene.

  • Fanconi_anemia (2151 variants)
  • Inborn_genetic_diseases (1730 variants)
  • not_provided (961 variants)
  • Premature_ovarian_failure_15 (309 variants)
  • Spermatogenic_failure_28 (298 variants)
  • FANCM-related_disorder (113 variants)
  • Hereditary_cancer-predisposing_syndrome (98 variants)
  • not_specified (85 variants)
  • Hereditary_breast_ovarian_cancer_syndrome (25 variants)
  • Hereditary_cancer (12 variants)
  • Fanconi_anemia_complementation_group_A (7 variants)
  • Fanconi_anemia,_complementation_group_M (3 variants)
  • Familial_cancer_of_breast (3 variants)
  • Hepatoblastoma (2 variants)
  • Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (1 variants)
  • Malignant_germ_cell_tumor_of_ovary (1 variants)
  • FANCM_Fanconi-like_genomic_instability_disorder (1 variants)
  • See_cases (1 variants)
  • Azoospermia (1 variants)
  • Hereditary_nonpolyposis_colorectal_carcinoma (1 variants)
  • Male_infertility_with_spermatogenesis_disorder (1 variants)
  • Retinoblastoma (1 variants)
  • Aplastic_anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020937.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
13
clinvar
730
clinvar
4
clinvar
 747
missense
3
clinvar
2
clinvar
2132
clinvar
91
clinvar
2
clinvar
 2230
nonsense
42
clinvar
29
clinvar
4
clinvar
 75
start loss
1
 1
frameshift
71
clinvar
33
clinvar
8
clinvar
 112
splice donor/acceptor (+/-2bp)
1
clinvar
23
clinvar
2
clinvar
1
clinvar
 27
Total 117 87 2160 822 6

Highest pathogenic variant AF is 0.00095478375

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FANCMprotein_codingprotein_codingENST00000267430 2364951
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.35e-151.0012535113961257480.00158
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.13210531.04e+31.010.000053013597
Missense in Polyphen154191.550.803982398
Synonymous-0.004953693691.000.00001913736
Loss of Function4.734087.90.4550.000004631176

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001730.00173
Ashkenazi Jewish0.000.00
East Asian0.0002180.000217
Finnish0.004760.00477
European (Non-Finnish)0.001510.00151
Middle Eastern0.0002180.000217
South Asian0.002030.00199
Other0.002120.00212

dbNSFP

Source: dbNSFP

Function
FUNCTION: DNA-dependent ATPase component of the Fanconi anemia (FA) core complex (PubMed:16116422). Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:16116422, PubMed:19423727, PubMed:20347428, PubMed:20347429). In complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA) and Holliday junction substrates (PubMed:20347428, PubMed:20347429). Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork. This activity is strongly stimulated in the presence of CENPS and CENPX (PubMed:20347429). In complex with FAAP24, efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates (PubMed:17289582). In vitro, on its own, strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA (PubMed:16116434). {ECO:0000269|PubMed:16116422, ECO:0000269|PubMed:16116434, ECO:0000269|PubMed:17289582, ECO:0000269|PubMed:19423727, ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429}.;
Pathway
Fanconi anemia pathway - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;Fanconi anemia pathway (Consensus)

Recessive Scores

pRec
0.163

Intolerance Scores

loftool
0.960
rvis_EVS
1.12
rvis_percentile_EVS
92.08

Haploinsufficiency Scores

pHI
0.0676
hipred
Y
hipred_score
0.508
ghis
0.539

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
N
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.516

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Fancm
Phenotype
liver/biliary system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cellular phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process
resolution of meiotic recombination intermediates;replication fork processing;DNA duplex unwinding;interstrand cross-link repair;nucleic acid phosphodiester bond hydrolysis;positive regulation of protein monoubiquitination
Cellular component
nucleoplasm;Fanconi anaemia nuclear complex;FANCM-MHF complex
Molecular function
DNA binding;chromatin binding;nuclease activity;protein binding;ATP binding;ATP-dependent 3'-5' DNA helicase activity