SEC63

Chr 6AD

SEC63 protein translocation regulator

Also known as: DNAJC23, ERdj2, PCLD2, PRO2507, SEC63L

NCBI Gene: 11231ENSG00000025796UniProt: Q9UGP8

The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC62 protein are found to be associated with ribosome-free SEC61 complex. It is speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER. The Sec61-Sec62-Sec63 complex might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome-dependent degradation pathway. The encoded protein is an integral membrane protein located in the rough ER. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Polycystic liver disease 2MIM #617004
AD
574
ClinVar variants
77
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEC63
🧬
Gene-Disease Validity (ClinGen)
polycystic liver disease 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
77 Pathogenic / Likely Pathogenic· 254 VUS of 574 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.57LOEUF
pLI 0.000
Z-score 4.07
OE 0.40 (0.28–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.20Z-score
OE missense 0.69 (0.62–0.76)
275 obs / 398.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.28–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.62–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 21 / 53.0Missense obs/exp: 275 / 398.6Syn Z: -0.06

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic33
VUS254
Likely Benign147
Benign85
Conflicting11
44
Pathogenic
33
Likely Pathogenic
254
VUS
147
Likely Benign
85
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
31
0
44
Likely Pathogenic
18
6
9
0
33
VUS
7
141
103
3
254
Likely Benign
0
8
97
42
147
Benign
0
2
76
7
85
Conflicting
—11
Total3815731652574

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

View in ClinVar →

Protein Context — Lollipop Plot

SEC63 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Polycystic liver disease 2

MIM #617004

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Spectrum of Polycystic Kidney and Liver Diseases and the Resulting Phenotypes.
Yang H et al.·Adv Kidney Dis Health
2023Review
Isolated polycystic liver disease genes define effectors of polycystin-1 function.
Besse W et al.·J Clin Invest
2017
Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease.
Chang AR et al.·JAMA
2022
Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease.
Mahboobipour AA et al.·Orphanet J Rare Dis
2024Review
Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease.
Schönauer R et al.·Gastroenterology
2024
Loss of heterozygosity is present in SEC63 germline carriers with polycystic liver disease.
Janssen MJ et al.·PLoS One
2012
Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management.
Cnossen WR et al.·Orphanet J Rare Dis
2014Review
Polycystic liver and kidney diseases.
Tahvanainen E et al.·Ann Med
2005Review
Extensive mutational analysis of PRKCSH and SEC63 broadens the spectrum of polycystic liver disease.
Waanders E et al.·Hum Mutat
2006
[Clinical and genetic analysis of autosomal dominant polycystic liver disease].
Su LS et al.·Zhonghua Gan Zang Bing Za Zhi
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools