ATP8B1

Chr 18ARAD

ATPase phospholipid transporting 8B1

Also known as: ATPIC, BRIC, FIC1, ICP1, PFIC, PFIC1

NCBI Gene: 5205ENSG00000081923UniProt: O43520

This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cholestasis, benign recurrent intrahepaticMIM #243300
AR
Cholestasis, intrahepatic, of pregnancy, 1MIM #147480
AD
Cholestasis, progressive familial intrahepatic 1MIM #211600
AR
UniProtCholestasis of pregnancy, intrahepatic 1
1278
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ATP8B1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 168 VUS of 1278 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.56LOEUF
pLI 0.000
Z-score 4.59
OE 0.41 (0.30–0.56)
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.
2.49Z-score
OE missense 0.73 (0.68–0.79)
515 obs / 700.8 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.0.41 (0.30–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.68–0.79)
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.1.02
0≤1.21.6
LoF obs/exp: 29 / 70.6Missense obs/exp: 515 / 700.8Syn Z: -0.23

ClinVar Variant Classifications

1278 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic38
VUS168
Likely Benign225
Benign6
Conflicting6
31
Pathogenic
38
Likely Pathogenic
168
VUS
225
Likely Benign
6
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
22
0
31
Likely Pathogenic
20
10
8
0
38
VUS
2
154
10
2
168
Likely Benign
0
6
97
122
225
Benign
0
0
5
1
6
Conflicting
—6
Total29172142125474

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

View in ClinVar →

Protein Context — Lollipop Plot

ATP8B1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ATP8B1-related intrahepatic cholestasis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cholestasis, benign recurrent intrahepatic

MIM #243300

Molecular basis of disorder known

Autosomal recessive

Cholestasis, intrahepatic, of pregnancy, 1

MIM #147480

Molecular basis of disorder known

Autosomal dominant

Cholestasis, progressive familial intrahepatic 1

MIM #211600

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular overview of progressive familial intrahepatic cholestasis.
Amirneni S et al.·World J Gastroenterol
2020Review
Systematic review of progressive familial intrahepatic cholestasis.
Baker A et al.·Clin Res Hepatol Gastroenterol
2019Review
Clinical phenotype of adult-onset liver disease in patients with variants in ABCB4, ABCB11, and ATP8B1.
Nayagam JS et al.·Hepatol Commun
2022Cohort
Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases.
Chen HL et al.·J Biomed Sci
2018Review
Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.
van Wessel DBE et al.·Hepatology
2021
Cholestatic liver disease.
Jüngst C et al.·Dig Dis
2013Review
ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.
Chang JC et al.·Liver Int
2025Functional
[Genetic cholestasis].
Ciocca M et al.·Arch Argent Pediatr
2009
Molecular Advances in Cholestatic Liver Diseases.
Memon R et al.·Adv Anat Pathol
2025Review
Histological evaluation in biliary diseases.
Saffioti F et al.·Curr Opin Gastroenterol
2023Review
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
PFIC - Progressive Familial Intrahepatic CholestasisAlagille Syndrome (ALGS)Cholestasis, Intrahepatic

Pediatric Evaluation and Registry for Liver Cholestasis in Canada

NOT YET RECRUITING
NCT07411716Children's Hospital of Eastern OntarioStarted 2026-03

External Resources

Links to major genomics databases and tools