TFCP2

protein-coding

transcription factor CP2

Gene summary

This gene encodes a transcription factor that binds the alpha-globin promoter and activates transcription of the alpha-globin gene. The encoded protein regulates erythroid gene expression, plays a role in the transcriptional switch of globin gene promoters, and it activates many other cellular and viral gene promoters. The gene product interacts with certain inflammatory response factors, and polymorphisms of this gene may be involved in the pathogenesis of Alzheimer's disease. [provided by RefSeq, Mar 2010]

MANE transcript

NM_005653.5

Inheritance

—

ClinVar variants

U:41

Top phenotype

TFCP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr12:51,093,656-51,173,135

External References & Databases

Ensembl (ENSG00000135457)

Transcript & Mutation Effects

hg38 • Region Span ~79.5 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 TFCP2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 33

TFCP2-related disorderTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005653.5. 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			35 clinvar			35
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	41	0	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005653.5	RefSeq	NP_005644.2	15	MANE Select
ENST00000257915.10	Ensembl	ENSP00000257915.5	15	MANE Select
NM_001173452.2	RefSeq	NP_001166923.1	15	Standard
NM_001173453.2	RefSeq	NP_001166924.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling events mediated by HDAC Class I

Biological Process

regulation of transcription by RNA polymerase II
mRNA transcription by RNA polymerase II
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
proximal promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding

Cellular Component

nucleus
nucleoplasm
cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257915
Coding exons: 15
Length: 79481
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125746
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.77	143	272	0.526	0.0000133	3333
Missense (PolyPhen)		22	72.501	0.30344		892
Synonymous	0.272	95	98.4	0.965	0.00000506	917
Loss of Function	3.04	15	34.2	0.439	0.00000186	364

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds a variety of cellular and viral promoters including fibrinogen, alpha-globin, SV40 and HIV-1 promoters. Activation of the alpha-globin promoter in erythroid cells is via synergistic interaction with UBP1 (By similarity). Functions as part of the SSP (stage selector protein) complex. Facilitates the interaction of the gamma-globin genes with enhancer elements contained in the locus control region in fetal erythroid cells. Interacts by binding to the stage selector element (SSE) in the proximal gamma-globin promoter. {ECO:0000250, ECO:0000269|PubMed:10455131, ECO:0000269|PubMed:1732747, ECO:0000269|PubMed:8035790, ECO:0000269|PubMed:8157699}.;

Recessive Scores

pRec: 0.247

Intolerance Scores

LoFtool: 0.792
RVIS EVS: -0.45
RVIS percentile EVS: 24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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