TCF23

protein-coding

transcription factor 23, the group of Basic helix-loop-helix proteins

Gene summary

The gene encodes a member of the basic helix-loop-helix transcription factor family. Studies of the orthologous gene in mouse have shown the encoded protein does not bind DNA but may negatively regulate other basic helix-loop-helix factors via the formation of a functionally inactive heterodimeric complex. [provided by RefSeq, May 2010]

MANE transcript

NM_175769.3

Inheritance

—

ClinVar variants

U:34B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr2:27,149,004-27,156,974

External References & Databases

Ensembl (ENSG00000163792)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TCF23 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 36

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_175769.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			34 clinvar	2 clinvar		36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	34	2	0	36

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_175769.3	RefSeq	NP_786951.1	3	MANE Select
ENST00000296096.6	Ensembl	ENSP00000296096.5	3	MANE Select
ENST00000968520.1	Ensembl	ENSP00000638579.1	2	Standard
ENST00000968520.2	Ensembl	ENSP00000638579.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
muscle organ development
positive regulation of gene expression
cell differentiation
decidualization

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
protein dimerization activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296096
Coding exons: 3
Length: 4507
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.761	115	140	0.819	0.00000936	1337
Missense (PolyPhen)		40	45.508	0.87897		425
Synonymous	0.0475	58	58.5	0.992	0.00000392	482
Loss of Function	0.302	7	7.92	0.884	4.87e-7	73

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00030	0.00025	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits E-box-mediated binding and transactivation of bHLH factors. Inhibitory effect is similar to that of ID proteins. Inhibits the formation of TCF3 and MYOD1 homodimers and heterodimers. Lacks DNA binding activity. Seems to play a role in the inhibition of myogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.330
RVIS EVS: 0.17
RVIS percentile EVS: 65.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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