TWIST2

twist family bHLH transcription factor 2, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 2:238848032-238910534

Links

ENSG00000233608 ∙ NCBI:117581 ∙ OMIM:607556 ∙ HGNC:20670 ∙ Uniprot:Q8WVJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ablepharon macrostomia syndrome (Strong), mode of inheritance: AD
• Barber-Say syndrome (Strong), mode of inheritance: AD
• focal facial dermal dysplasia type III (Strong), mode of inheritance: AR
• ablepharon macrostomia syndrome (Supportive), mode of inheritance: AD
• Barber-Say syndrome (Supportive), mode of inheritance: AD
• focal facial dermal dysplasia type III (Supportive), mode of inheritance: AD
• ablepharon macrostomia syndrome (Definitive), mode of inheritance: AD
• focal facial dermal dysplasia type III (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ablepharon-macrostomia syndrome; Barber-Say syndrome; Focal facial dermal dysplasia 3, Setleis type	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dermatologic; Musculoskeletal	1867254; 2036354; 3631024; 4412216; 8368246; 8746822; 8818454; 11038439; 11807864; 12210295; 15103726; 16650233; 14069095; 20799330; 20830793; 20691403; 21801849; 21931173; 26119818

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TWIST2 gene.

• not_provided (15 variants)
• Inborn_genetic_diseases (15 variants)
• Focal_facial_dermal_dysplasia_type_III (3 variants)
• Barber-Say_syndrome (3 variants)
• TWIST2-related_disorder (2 variants)
• Ablepharon_macrostomia_syndrome (1 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TWIST2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001271893.4. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	6		7
missense	3		21			24
nonsense	2		1			3
start loss						0
frameshift	1					1
splice donor/acceptor (+/-2bp)						0
Total	6	0	23	6	0

Highest pathogenic variant AF is 0.0000056867007

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TWIST2	protein_coding	protein_coding	ENST00000448943	1	39221

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.13	33	89.9	0.367	0.00000412	1042
Missense in Polyphen		3	28.928	0.10371		354
Synonymous	1.88	25	40.2	0.622	0.00000191	311
Loss of Function	1.46	0	2.49	0.00	1.06e-7	33

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the E-box consensus sequence 5'-CANNTG-3' as a heterodimer and inhibits transcriptional activation by MYOD1, MYOG, MEF2A and MEF2C. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Involved in postnatal glycogen storage and energy metabolism (By similarity). Inhibits the premature or ectopic differentiation of preosteoblast cells during osteogenesis, possibly by changing the internal signal transduction response of osteoblasts to external growth factors. {ECO:0000250, ECO:0000269|PubMed:11062344}.
• Disease: DISEASE: Ablepharon-macrostomia syndrome (AMS) [MIM:200110]: A congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth. {ECO:0000269|PubMed:26119818}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Barber-Say syndrome (BBRSAY) [MIM:209885]: A rare ectodermal dysplasia characterized by ectropion, macrostomia, ear abnormalities, broad nasal bridge, bulbous nose, redundant skin, hypertrichosis, dental abnormalities, and variable other features. {ECO:0000269|PubMed:26119818}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteoglycans in cancer - Homo sapiens (human);EMT transition in Colorectal Cancer;Transcriptional regulation by RUNX2;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription (Consensus)

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: multicellular organism development;cell differentiation;positive regulation of cell migration;negative regulation of apoptotic process;negative regulation of osteoblast differentiation;negative regulation of transcription, DNA-templated
• Cellular component: nucleus;nucleolus;cytoplasm
• Molecular function: DNA binding;protein binding;protein dimerization activity