PHF20L1

Chr 8

PHD finger protein 20 like 1

Also known as: CGI-72, TDRD20B, URLC1

The PHF20L1 protein binds methylated proteins and negatively regulates their proteasomal degradation, including key regulators like DNMT1 and SOX2. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.187). This gene is associated with neurodevelopmental disorders affecting cognitive function and early development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.19
Clinical SummaryPHF20L1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 96 VUS of 182 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 6.33
OE 0.09 (0.040.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.85Z-score
OE missense 0.78 (0.720.84)
418 obs / 538.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.19)
00.351.4
Missense OE0.78 (0.720.84)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 5 / 56.3Missense obs/exp: 418 / 538.5Syn Z: -0.10
DN
0.3196th %ile
GOF
0.2995th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

182 submitted variants in ClinVar

Classification Summary

Pathogenic54
VUS96
Likely Benign2
Benign1
54
Pathogenic
96
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
0
0
0
VUS
0
87
9
0
96
Likely Benign
0
2
0
0
2
Benign
0
0
0
1
1
Total089631153

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

View in ClinVar →

Protein Context — Lollipop Plot

PHF20L1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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