CTDSP2

protein-coding

CTD small phosphatase 2, the group of CTD family phosphatases|MicroRNA protein coding host genes

Gene summary

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in protein dephosphorylation. Predicted to be located in nucleoplasm. Predicted to be part of TIM23 mitochondrial import inner membrane translocase complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_005730.4

Inheritance

—

ClinVar variants

U:26B:5

Top phenotype

CTDSP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr12:57,819,927-57,846,729

External References & Databases

Ensembl (ENSG00000175215)

Transcript & Mutation Effects

hg38 • Region Span ~26.8 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 CTDSP2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 20

CTDSP2-related disorderTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005730.4. 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				5 clinvar		5
missense			21 clinvar			21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	26	5	0	31

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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_005730.4	RefSeq	NP_005721.3	8	MANE Select
ENST00000398073.7	Ensembl	ENSP00000381148.2	8	MANE Select
ENST00000547701.5	Ensembl	ENSP00000446705.1	3	Standard
ENST00000547701.6	Ensembl	ENSP00000446705.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-Ncore
XBP1(S) activates chaperone genes
BMP receptor signaling
Coregulation of Androgen receptor activity
Regulation of cytoplasmic and nuclear SMAD2/3 signaling

Biological Process

negative regulation of protein phosphorylation
regulation of transcription by RNA polymerase II
protein dephosphorylation
IRE1-mediated unfolded protein response
negative regulation of G1/S transition of mitotic cell cycle

Molecular Function

phosphoprotein phosphatase activity
protein binding
RNA polymerase II CTD heptapeptide repeat phosphatase activity
metal ion binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398073
Coding exons: 8
Length: 26813
Individuals with no LoFs: 124857
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 124864
p: 0.0000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	107	161	0.666	0.00000913	1761
Missense (PolyPhen)		23	60.721	0.37878		693
Synonymous	0.796	56	64.1	0.873	0.00000365	537
Loss of Function	2.43	4	13.7	0.291	5.81e-7	165

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Preferentially catalyzes the dephosphorylation of 'Ser- 5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. May contribute to the development of sarcomas. {ECO:0000269|PubMed:12721286, ECO:0000269|PubMed:15681389}.;

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.464
RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.968

Gene Damage Prediction

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