HFM1 (helicase for meiosis 1)

Gene

• Entrez ID: 164045
• Gene name: Helicase for meiosis 1
• Gene symbol: HFM1
• Synonyms (NCBI Gene): MER3, POF9, SEC63D1, Si-11, Si-11-6, helicase
• Chromosome: 1
• Chromosome location: 1p22.2
• Summary: The protein encoded by this gene is thought to be an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. Defects in this gene are a cause of premature ovarian failure 9 (POF9). [provided by RefSeq, Apr 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587777268	A>C	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant, intron variant, genic downstream transcript variant, 3 prime UTR variant
rs587777269	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant, intron variant
rs587777270	GG>C	Pathogenic	Frameshift variant, non coding transcript variant, intron variant, genic downstream transcript variant, coding sequence variant
rs730880018	C>G	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017476	hsa-miR-335-5p	Microarray	18185580
MIRT022487	hsa-miR-124-3p	Microarray	18668037
MIRT635717	hsa-miR-551b-5p	HITS-CLIP	23824327
MIRT635716	hsa-miR-181a-5p	HITS-CLIP	23824327
MIRT635715	hsa-miR-181b-5p	HITS-CLIP	23824327
MIRT635714	hsa-miR-181c-5p	HITS-CLIP	23824327
MIRT635713	hsa-miR-181d-5p	HITS-CLIP	23824327
MIRT635712	hsa-miR-4262	HITS-CLIP	23824327
MIRT635711	hsa-miR-4724-5p	HITS-CLIP	23824327
MIRT635710	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT635717	hsa-miR-551b-5p	HITS-CLIP	23824327
MIRT635711	hsa-miR-4724-5p	HITS-CLIP	23824327
MIRT635710	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT635717	hsa-miR-551b-5p	HITS-CLIP	23824327
MIRT635716	hsa-miR-181a-5p	HITS-CLIP	23824327
MIRT635715	hsa-miR-181b-5p	HITS-CLIP	23824327
MIRT635714	hsa-miR-181c-5p	HITS-CLIP	23824327
MIRT635713	hsa-miR-181d-5p	HITS-CLIP	23824327
MIRT635712	hsa-miR-4262	HITS-CLIP	23824327
MIRT635711	hsa-miR-4724-5p	HITS-CLIP	23824327
MIRT635710	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT440510	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT440510	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT635717	hsa-miR-551b-5p	HITS-CLIP	23824327
MIRT635716	hsa-miR-181a-5p	HITS-CLIP	23824327
MIRT635715	hsa-miR-181b-5p	HITS-CLIP	23824327
MIRT635714	hsa-miR-181c-5p	HITS-CLIP	23824327
MIRT635713	hsa-miR-181d-5p	HITS-CLIP	23824327
MIRT635712	hsa-miR-4262	HITS-CLIP	23824327
MIRT635711	hsa-miR-4724-5p	HITS-CLIP	23824327
MIRT635710	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT635717	hsa-miR-551b-5p	HITS-CLIP	23824327
MIRT635711	hsa-miR-4724-5p	HITS-CLIP	23824327
MIRT635710	hsa-miR-2681-5p	HITS-CLIP	23824327
MIRT635717	hsa-miR-551b-5p	HITS-CLIP	23824327
MIRT635716	hsa-miR-181a-5p	HITS-CLIP	23824327
MIRT635715	hsa-miR-181b-5p	HITS-CLIP	23824327
MIRT635714	hsa-miR-181c-5p	HITS-CLIP	23824327
MIRT635713	hsa-miR-181d-5p	HITS-CLIP	23824327
MIRT635712	hsa-miR-4262	HITS-CLIP	23824327
MIRT635711	hsa-miR-4724-5p	HITS-CLIP	23824327
MIRT635710	hsa-miR-2681-5p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000712	Process	Resolution of meiotic recombination intermediates	IBA
GO:0000712	Process	Resolution of meiotic recombination intermediates	IEA
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003678	Function	DNA helicase activity	IBA
GO:0004386	Function	Helicase activity	IEA
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0007131	Process	Reciprocal meiotic recombination	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016853	Function	Isomerase activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051321	Process	Meiotic cell cycle	IEA

Other IDs

• MIM: 615684
• HGNC: 20193
• e!Ensembl: ENSG00000162669

Protein

• UniProt ID: A2PYH4
• Protein name: Probable ATP-dependent DNA helicase HFM1 (EC 5.6.2.4) (DNA 3'-5' helicase HFM1) (SEC63 domain-containing protein 1)
• Protein function: Required for crossover formation and complete synapsis of homologous chromosomes during meiosis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00270	DEAD	282 → 467	DEAD/DEAH box helicase	Domain
  PF00271	Helicase_C	514 → 659	Helicase conserved C-terminal domain	Family
  PF02889	Sec63	777 → 1091	Sec63 Brl domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Preferentially expressed in testis and ovary. {ECO:0000269|PubMed:17286053}.
• Sequence:

  MLKSNDCLFSLENLFFEKPDEVENHPDNEKSLDWFLPPAPLISEIPDTQELEEELESHKL
  LGQEKRPKMLTSNLKITNEDTNYISLTQKFQFAFPSDKYEQDDLNLEGVGNNDLSHIAGK
  LTYASQKYKNHIGTEIAPEKSVPDDTKLVNFAEDKGESTSVFRKRLFKISDNIHGSAYSN
  DNELDSHIGSVKIVQTEMNKGKSRNYSNSKQKFQYSANVFTANNAFSASEIGEGMFKAPS
  FSVAFQPHDIQEVTENGLGSLKAVTEIPAKFRSIFKEFPYFNYIQSKAFDDLLYTDRNFV
  ICAPTGSGKTVVFELAITRLLMEVPLPWLNIKIVYMAPIKALCSQRFDDWKEKFGPIGLN
  CKELTGDTVMDDLFEIQHAHIIMTTPEKWDSMTRKWRDNSLVQLVRLFLIDEVHIVKDEN
  RGPTLEVVVSRMKTVQSVSQTLKNTSTAIPMRFVAVSATIPNAEDIAEWLSDGERPAVCL
  KMDESHRPVKLQKVVLGFPCSSNQTEFKFDLTLNYKIASVIQMYSDQKPTLVFCATRKGV
  QQAASVLVKDAKFIMTVEQKQRLQKYAYSVRDSKLRDILKDGAAYHHAGMELSDRKVVEG
  AFTVGDLPVLFTTSTLAMGVNLPAHLVVIKSTMHYAGGLFEEYSETDILQMIGRAGRPQF
  DTTATAVIMTRLSTRDKYIQMLACRDTVESSLHRHLIEHLNAEIVLHTITDVNIAVEWIR
  STLLYIRALKNPSHYGFASGLNKDGIEAKLQELCLKNLNDLSSLDLIKMDEGVNFKPTEA
  GRLMAWYYITFETVKKFYTISGKETLSDLVTLIAGCKEFLDIQLRINEKKTLNTLNKDPN
  RITIRFPMEGRIKTREMKVNCLIQAQLGCIPIQDFALTQDTAKIFRHGSRITRWLSDFVA
  AQEKKFAVLLNSLILAKCFRCKLWENSLHVSKQLEKIGITLSNAIVNAGLTSFKKIEETD
  ARELELILNRHPPFGTQIKETVMYLPKYELKVEQITRYSDTTAEILVTVILRNFEQLQTK
  RTASDSHYVTLIIGDADNQVVYLHKITDSVLLKAGSWAKKIAVKRALKSEDLSINLISSE
  FVGLDIQQKLTVFYLEPKRFGNQITMQRKSETQISHSKHSDISTIAGPNKGTTASKKPGN
  RECNHLCKSKHTCGHDCCKIGVAQKSEIKESTISSYLSDLRNRNAVSSVPPVKRLKIQMN
  KSQSVDLKEFGFTPKPSLPSISRSEYLNISELPIMEQWDQPEIYGKVRQEPSEYQDKEVL
  NVNFELGNEVWDDFDDENLEVTSFSTDTEKTKISGFGNTLSSSTRGSKLPLQESKSKFQR
  EMSNSFVSSHEMSDISLSNSAMPKFSASSMTKLPQQAGNAVIVHFQERKPQNLSPEIEKQ
  CFTFSEKNPNSSNYKKVDFFIRNSECKKEVDFSMYHPDDEADEMKSLLGIFDGIF

• Sequence length: 1435

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Azoospermia	Pathogenic	rs746229304	RCV001797566	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Genetic non-acquired premature ovarian failure	Pathogenic; Likely pathogenic	rs2101730664, rs1209622397	RCV001661768 RCV001661769	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian failure 9	Likely pathogenic; Pathogenic	rs763964671, rs730880018, rs587777268, rs587777269, rs587777270, rs763202322, rs2525301718, rs754924716, rs751622198	RCV001839424 RCV000114368 RCV000114369 RCV000114370 RCV000114371 RCV005361734 RCV003146003 RCV003388778 RCV001290508	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Spermatogenic failure 4	Pathogenic	rs748343941, rs753422559	RCV002261380 RCV002261381	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HFM1-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL OR BEHAVIOURAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Azoospermia	Azoospermia	Pubtator	34429122, 35172124, 37574498	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Azoospermia Nonobstructive	Nonobstructive azoospermia	Pubtator	35486194	Associate	★☆☆☆☆ Found in Text Mining only
Bloom Syndrome	Bloom syndrome	Pubtator	11472631, 12724401, 12975363, 17878217, 19632996, 21300576, 22024395	Associate	★☆☆☆☆ Found in Text Mining only
Bloom Syndrome	Bloom Syndrome	BEFREE	12060858, 17407155, 20663905, 26984941		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	16430786		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26125302	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	33042264	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	29572031	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Small Cell	Small cell carcinoma	Pubtator	36379381	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	20817850		★☆☆☆☆ Found in Text Mining only
Cockayne Syndrome	Cockayne Syndrome	BEFREE	16947863, 28276523		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	12214280		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	19161603	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	31422817	Associate	★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of radius	Congenital Hypoplasia Of Radius	BEFREE	15897384		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	37198333	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	10495473, 22110093		★☆☆☆☆ Found in Text Mining only
Endocrine System Diseases	Endocrine system disease	Pubtator	37198333	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	36708047	Inhibit	★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi anemia	Pubtator	22024395	Associate	★☆☆☆☆ Found in Text Mining only
Graves Disease	Graves Disease	BEFREE	18026693		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	37198333	Associate	★☆☆☆☆ Found in Text Mining only
Hoyeraal Hreidarsson syndrome	Hoyeraal hreidarsson syndrome	Pubtator	37853975	Associate	★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	35486194	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	31422817	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	BEFREE	10495473		★☆☆☆☆ Found in Text Mining only
Kidney Failure, Acute	Kidney Failure	BEFREE	30175410		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	28234905, 29930297		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	16430786		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	16914751, 20663905, 23161009, 27102626, 28276523		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	10820291, 31573152	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	37198333	Associate	★☆☆☆☆ Found in Text Mining only
Microphthalmia Syndromic 6	Microphthalmia	Pubtator	23797032	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	9021029		★☆☆☆☆ Found in Text Mining only
Myositis	Myositis	BEFREE	28720599		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	21700224	Associate	★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Primary ovarian failure	Ovarian Failure	Orphanet			★☆☆☆☆ Found in Text Mining only
Orofaciodigital Syndrome I	Orofaciodigital Syndrome	BEFREE	28711741		★☆☆☆☆ Found in Text Mining only
Orofaciodigital Syndromes	Orofaciodigital syndrome	BEFREE	28711741		★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian diseases	Pubtator	35881270	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	26679638, 31279343		★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	GENOMICS_ENGLAND_DG	26679638		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	18953434, 23951333	Associate	★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	BEFREE	26679638, 31279343		★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	HPO_DG			★☆☆☆☆ Found in Text Mining only
PREMATURE OVARIAN FAILURE 9	Premature Ovarian Failure	UNIPROT_DG	24597873		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PREMATURE OVARIAN FAILURE 9	Premature Ovarian Failure	GENOMICS_ENGLAND_DG	26679638		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PREMATURE OVARIAN FAILURE 9	Premature Ovarian Failure	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PREMATURE OVARIAN FAILURE 9	Premature Ovarian Failure	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progeria	Progeria	BEFREE	22127259		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	21045146, 36499126	Associate	★☆☆☆☆ Found in Text Mining only
Rapadilino syndrome	Rapadilino Syndrome	BEFREE	15897384		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	23045696, 27072132	Associate	★☆☆☆☆ Found in Text Mining only
Rothmund-Thomson syndrome	Rothmund-Thomson Syndrome	BEFREE	10678659, 12952869, 15897384, 20113479		★☆☆☆☆ Found in Text Mining only
Seckel syndrome 1	Seckel syndrome	Pubtator	31045292	Associate	★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	20613862	Associate	★☆☆☆☆ Found in Text Mining only
Spinal muscular atrophy with respiratory distress 1	Spinal muscular atrophy	Pubtator	22965130	Associate	★☆☆☆☆ Found in Text Mining only
Spinocerebellar ataxia autosomal recessive 1	Spinocerebellar ataxia	Pubtator	32686621	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	38489268	Associate	★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	24496236		★☆☆☆☆ Found in Text Mining only
Urogenital Abnormalities	Urogenital abnormalities	Pubtator	37198333	Associate	★☆☆☆☆ Found in Text Mining only
Werner Syndrome	Werner Syndrome	BEFREE	10678659, 11287731, 11316787, 11498731, 12242278, 19306876, 21464516, 22127259, 26984941, 28276523, 29752965, 9048918, 9856481		★☆☆☆☆ Found in Text Mining only
Werner Syndrome	Werner syndrome	Pubtator	15292449, 17015833, 17378750, 17911100, 20103920, 20157511, 20157518, 23849162, 28069813, 35751457	Associate	★☆☆☆☆ Found in Text Mining only
Xeroderma Pigmentosum	Xeroderma Pigmentosum	BEFREE	9171087		★☆☆☆☆ Found in Text Mining only
Xeroderma Pigmentosum, Complementation Group D	Xeroderma Pigmentosum	BEFREE	26086338		★☆☆☆☆ Found in Text Mining only
XFE Progeroid Syndrome	XFE Progeroid Syndrome	BEFREE	22127259		★☆☆☆☆ Found in Text Mining only