TCFL5

protein-coding

transcription factor like 5, the group of Basic helix-loop-helix proteins

Gene summary

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; regulation of cell population proliferation; and spermatogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006602.4

Inheritance

—

ClinVar variants

P:1U:87B:2

Top phenotype

Oligoasthenoteratozoospermia

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr20:62,841,005-62,861,822

External References & Databases

Ensembl (ENSG00000101190)

Transcript & Mutation Effects

hg38 • Region Span ~20.8 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 TCFL5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 2

OligoasthenoteratozoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006602.4. 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				1 clinvar		1
missense		1 clinvar	85 clinvar	1 clinvar		87
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	87	2	0	90

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006602.4	RefSeq	NP_006593.2	6	MANE Select
ENST00000335351.8	Ensembl	ENSP00000334294.3	6	MANE Select
NM_001301726.2	RefSeq	NP_001288655.1	6	Standard
ENST00000217162.5	Ensembl	ENSP00000217162.5	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription, DNA-templated
transcription by RNA polymerase II
multicellular organism development
spermatogenesis

Molecular Function

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

Cellular Component

male germ cell nucleus
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335351
Coding exons: 6
Length: 20649
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125742
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	157	201	0.782	0.0000109	3165
Missense (PolyPhen)		58	93.485	0.62042		1245
Synonymous	-0.385	88	83.5	1.05	0.00000501	1064
Loss of Function	3.78	1	18.6	0.0537	0.00000112	216

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative transcription factor. Isoform 3 may play a role in early spermatogenesis. {ECO:0000269|PubMed:9763657}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.826

Gene Damage Prediction

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