THAP12

protein-coding

THAP domain containing 12, the group of THAP domain containing

Gene summary

Predicted to enable several functions, including DNA binding activity; protein dimerization activity; and zinc ion binding activity. Predicted to be involved in negative regulation of cell population proliferation and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

PRKRIR

MANE transcript

NM_004705.4

Inheritance

ClinVar variants

U:11B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr11:76,349,898-76,381,132

External References & Databases

Ensembl (ENSG00000137492)

Transcript & Mutation Effects

hg38 • Region Span ~31.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0800439

Submitter: Broad Center for Mendelian Genomics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THAP12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 5

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004705.4. 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 clinvar		2
missense			8 clinvar			8
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	11	1	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004705.4	RefSeq	NP_004696.2	5	MANE Select
ENST00000260045.8	Ensembl	ENSP00000260045.3	5	MANE Select
ENST00000528993.5	Ensembl	ENSP00000433966.1	3	Standard
ENST00000682046.1	Ensembl	ENSP00000508120.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
signal transduction
negative regulation of cell population proliferation

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260045
Coding exons: 5
Length: 31016
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125740
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.34	251	379	0.662	0.0000188	5030
Missense (PolyPhen)		15	52.685	0.28471		823
Synonymous	0.366	137	143	0.961	0.00000744	1422
Loss of Function	4.24	4	28.3	0.141	0.00000174	358

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000085	0.000079	rare
South Asian	0.000067	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Upstream regulator of interferon-induced serine/threonine protein kinase R (PKR). May block the PKR- inhibitory function of DNAJC3, resulting in restoration of kinase activity and suppression of cell growth.;

Recessive Scores

pRec: 0.201

Intolerance Scores

RVIS EVS: -0.56
RVIS percentile EVS: 19.73

Essentials

Essential (gene trap): E