CTDP1

Chr 18AR

CTD phosphatase subunit 1

Also known as: CCFDN, FCP1

NCBI Gene: 9150 ENSG00000060069 UniProt: Q9Y5B0 OMIM: 604927

This gene encodes a phosphatase that dephosphorylates the C-terminal domain of RNA polymerase II to promote transcription initiation and also dephosphorylates key substrates required for mitotic exit. Mutations cause congenital cataracts, facial dysmorphism, and neuropathy (CCFDN), an autosomal recessive disorder with early-onset features affecting the eyes, craniofacial development, and peripheral nervous system. The gene is highly intolerant to loss-of-function variants (LOEUF 0.529), indicating strong selective pressure against haploinsufficiency.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF, and functions as a phosphatase that processively dephosphorylates the C-terminus of POLR2A (a subunit of RNA polymerase II), making it available for initiation of gene expression. Mutations in this gene are associated with congenital cataracts, facial dysmorphism and neuropathy syndrome (CCFDN). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.531 OMIM phenotype

Clinical Summary— CTDP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 295 VUS of 713 total submissions

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GeneReview available — CTDP1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.001

Z-score 3.86

OE 0.33 (0.22–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.00Z-score

OE missense 0.88 (0.82–0.95)

501 obs / 567.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.22–0.53)

0≤0.351.4

Missense OE?0.88 (0.82–0.95)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 13 / 39.0Missense obs/exp: 501 / 567.8Syn Z: -1.50

ClinVar Variant Classifications

713 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS295

Likely Benign327

Benign70

Conflicting12

Pathogenic

295

VUS

327

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	8	271	15	1	295
Likely Benign	1	39	123	164	327
Benign	0	8	46	16	70
Conflicting	—				12
Total	9	318	185	181	705

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

165 pathogenic / likely-pathogenic (of 196) ClinVar copy-number / structural variants overlap CTDP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →