BHLHA9 (basic helix-loop-helix family member a9)

Gene

• Entrez ID: 727857
• Gene name: Basic helix-loop-helix family member a9
• Gene symbol: BHLHA9
• Synonyms (NCBI Gene): BHLHF42, CCSPD
• Chromosome: 17
• Chromosome location: 17p13.3
• Summary: This gene is a member of the basic helix-loop-helix family. The encoded protein is a transcription factor involved in limb development. Mutations in this gene have been associated with mesoaxial synostotic syndactyly Malik-Percin type (MSSD). Copy number

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs672601337	A>G	Pathogenic	Coding sequence variant, missense variant
rs672601338	G>C	Pathogenic	Coding sequence variant, missense variant
rs672601339	G>T	Pathogenic	Coding sequence variant, missense variant
rs886037856	GA>TT	Likely-pathogenic	Missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0003677	Function	DNA binding	IEA
GO:0005515	Function	Protein binding	IPI	25466284, 32296183
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	25466284
GO:0005737	Component	Cytoplasm	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0032502	Process	Developmental process	IBA
GO:0046982	Function	Protein heterodimerization activity	IDA	25466284
GO:0046983	Function	Protein dimerization activity	IEA

Other IDs

• MIM: 615416
• HGNC: 35126
• e!Ensembl: ENSG00000205899

Protein

• UniProt ID: Q7RTU4
• Protein name: Class A basic helix-loop-helix protein 9 (bHLHa9) (Class F basic helix-loop-helix factor 42) (bHLHf42)
• Protein function: Transcription factor, which play a role in limb development. Is an essential player in the regulatory network governing transcription of genes implicated in limb morphogenesis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00010	HLH	66 → 118	Helix-loop-helix DNA-binding domain	Domain

• Sequence:

  MLRGAPGLGLTARKGAEDSAEDLGGPCPEPGGDSGVLGANGASCSRGEAEEPAGRRRARP
  VRSKARRMAANVRERKRILDYNEAFNALRRALRHDLGGKRLSKIATLRRAIHRIAALSLV
  LRASPAPRGPCGHLECHGPAARGDTGDTGASPPPPAGPSLARPDAARPSVPSAPRCASCP
  PHAPLARPSAVAEGPGLAQASGGSWRRCPGASSAGPPPWPRGYLRSAPGMGHPRS

• Sequence length: 235

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
Camptosynpolydactyly, complex	Likely pathogenic	rs886037856	RCV000239477	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mesoaxial synostotic syndactyly with phalangeal reduction	Pathogenic; Likely pathogenic	rs672601337, rs672601338, rs672601339	RCV000149486 RCV000149487 RCV000149488 RCV003990948	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BHLHA9-related disorder	Benign; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOLLOP-WOLFGANG COMPLEX	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT-HAND-FOOT MALFORMATION WITH LONG BONE DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLIT-HAND/FOOT MALFORMATION WITH LONG BONE DEFICIENCY 1	—	Disgenet, GenCC Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYNDACTYLY, MESOAXIAL SYNOSTOTIC, WITH PHALANGEAL REDUCTION	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
2-3 toe syndactyly	Syndactyly Of The Toes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	23035971	Associate	★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar disorder	Pubtator	23035971	Associate	★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Camptosynpolydactyly, Complex	Camptosynpolydactyly	UNIPROT_DG	27041388		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Camptosynpolydactyly, Complex	Camptosynpolydactyly	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Camptosynpolydactyly, Complex	Camptosynpolydactyly	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Hand Deformities	Congenital anomaly of the hand	BEFREE	26549411		★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of femur	Short femur	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital omphalocele	Congenital omphalocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	23035971	Associate	★☆☆☆☆ Found in Text Mining only
Ectrodactyly	Ectrodactyly	BEFREE	22147889, 23790188, 24852374		★☆☆☆☆ Found in Text Mining only
Ectrodactyly	Ectrodactyly	Pubtator	25351291	Associate	★☆☆☆☆ Found in Text Mining only
Ectrodactyly	Ectrodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Femur bifid with monodactylous ectrodactyly	Gollop-Wolfgang complex	BEFREE	25351291		★☆☆☆☆ Found in Text Mining only
Femur bifid with monodactylous ectrodactyly	Gollop-Wolfgang complex	ORPHANET_DG	25351291		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	23035971		★☆☆☆☆ Found in Text Mining only
Gollop-Wolfgang complex	Gollop-Wolfgang Complex	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplasia of thumb	Hypoplasia Of Thumb	HPO_DG			★☆☆☆☆ Found in Text Mining only
Limb Deformities, Congenital	Congenital anomaly of limb	BEFREE	23202277, 24852374, 25351291		★☆☆☆☆ Found in Text Mining only
Poliosis	Poliosis	BEFREE	28324176		★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	GENOMICS_ENGLAND_DG	22147889		★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	BEFREE	30107244, 31152918		★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polydactyly preaxial type 1	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Split hand foot deformity 1	Split hand foot deformity	BEFREE	22147889, 23790188, 24852374		★☆☆☆☆ Found in Text Mining only
Split-Hand-Foot Malformation With Long Bone Deficiency 1	Split-Hand-Foot Malformation With Long Bone Deficiency	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Split-Hand-Foot Malformation With Sensorineural Hearing Loss	Split-Hand-Foot Malformation With Sensorineural Hearing Loss	GENOMICS_ENGLAND_DG	22147889		★☆☆☆☆ Found in Text Mining only
Syndactyly	Syndactyly	BEFREE	24852374, 28324176, 30107244, 31152918		★☆☆☆☆ Found in Text Mining only
Syndactyly Mesoaxial Synostotic with Phalangeal Reduction	Syndactyly	Pubtator	25466284	Associate	★☆☆☆☆ Found in Text Mining only
Syndactyly of fingers	Syndactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Syndactyly of the toes	Syndactyly Of The Toes	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	GENOMICS_ENGLAND_DG	22147889		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	BEFREE	25466284		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	ORPHANET_DG	25466284		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	UNIPROT_DG	25466284		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tibial aplasia-ectrodactyly syndrome	Tibial Aplasia-Ectrodactyly Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Ulnar polydactyly of fingers	Postaxial hand polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only