| Subtype / common name | Causal gene / protein | Core molecular defect | Expected GGT pattern | Typical onset / key phenotype and extrahepatic clues | Prognosis / cancer or treatment-response notes |
|---|---|---|---|---|---|
| PFIC1 / FIC1 deficiency | **ATP8B1** / FIC1 (aminophospholipid flippase) | Loss of canalicular membrane lipid asymmetry and stability, impairing bile formation and promoting bile-acid toxicity (pqac-00000005, pqac-00000011, pqac-00000029) | Usually **low/normal** (pqac-00000005, pqac-00000021) | Neonatal or early-infantile cholestasis with jaundice, severe pruritus, hepatosplenomegaly, failure to thrive; extrahepatic clues include diarrhea, pancreatic insufficiency, short stature, elevated sweat chloride, sensorineural hearing loss (pqac-00000005, pqac-00000011, pqac-00000021) | Progressive disease; native-liver survival improved when serum bile acids fall after diversion; residual extrahepatic disease may persist after transplant, including diarrhea/steatosis (pqac-00000004, pqac-00000016) |
| PFIC2 / BSEP deficiency | **ABCB11** / BSEP | Defective canalicular bile-salt export causing intracellular bile-salt retention and hepatocyte injury (pqac-00000005, pqac-00000027, pqac-00000029) | Usually **low/normal** (pqac-00000005, pqac-00000016) | Early infancy; severe pruritus, cholestasis, rapid progression; genotype-defined severity spectrum with residual vs absent BSEP expression/function (pqac-00000003, pqac-00000017) | Generally the most severe common form; higher HCC risk, especially biallelic truncating / severe BSEP groups; poorer response to biliary diversion and IBAT inhibitors when BSEP is absent; risk of antibody-induced BSEP deficiency after transplant (pqac-00000002, pqac-00000003, pqac-00000004, pqac-00000016, pqac-00000017) |
| PFIC3 / MDR3 deficiency | **ABCB4** / MDR3 | Impaired phosphatidylcholine secretion into bile, leaving bile acids insufficiently buffered and injuring cholangiocytes/hepatocytes (pqac-00000009, pqac-00000023, pqac-00000029) | Usually **high** (pqac-00000009, pqac-00000016) | Often later infancy, childhood, adolescence, or adulthood; cholestasis with portal fibrosis and bile duct proliferation; heterozygotes may have milder phenotypes such as transient neonatal cholestasis, cholelithiasis, ICP, or drug-induced cholestasis (pqac-00000009, pqac-00000033) | Variable expressivity; carcinogenesis including cholangiocarcinoma/HCC reported in severe disease; generally not the main low-GGT/IBAT-responsive archetype (pqac-00000009, pqac-00000033) |
| PFIC4 / TJP2 deficiency | **TJP2** / tight junction protein 2 (ZO-2) | Tight-junction failure with claudin-1 mislocalization and paracellular reflux of toxic bile acids from canaliculi (pqac-00000009, pqac-00000024) | Usually **low/normal** (pqac-00000009, pqac-00000016) | Often severe neonatal/infantile cholestasis; giant-cell transformation on histology; some patients have respiratory or neurologic features; phenotype can range from self-limited to progressive liver disease (pqac-00000009, pqac-00000024) | Increased HCC risk reported even in infancy; close surveillance recommended; severity variable across families (pqac-00000009, pqac-00000018, pqac-00000033) |
| PFIC5 / FXR deficiency | **NR1H4** / FXR | Loss of bile-acid sensing/transcriptional control, with impaired **ABCB11/BSEP** induction and defective repression of bile-acid synthesis (pqac-00000009, pqac-00000024, pqac-00000034) | Usually **low/normal** (pqac-00000009, pqac-00000018) | Neonatal cholestasis with markedly elevated bile acids; characteristic early coagulopathy that may be vitamin K-unresponsive; often high AFP (pqac-00000009, pqac-00000018, pqac-00000034) | Usually rapidly progressive with early liver failure and need for transplant; very rare (pqac-00000009, pqac-00000033) |
| MYO5B-related PFIC / isolated MYO5B cholestasis / “PFIC6” in some sources | **MYO5B** / myosin Vb | Rab11-dependent apical trafficking defect causing BSEP/MDR3 mislocalization away from the canalicular membrane; epithelial polarity defect (pqac-00000009, pqac-00000024, pqac-00000025) | Usually **low/normal** (pqac-00000018, pqac-00000022) | Infancy or early childhood; may present as isolated cholestasis, microvillus inclusion disease, or both; extrahepatic clue is intractable diarrhea/enteropathy when intestinal disease is present (pqac-00000009, pqac-00000018, pqac-00000022) | Post-intestinal-transplant cholestasis can worsen; combined liver-intestinal strategies or diversion may be needed in selected cases; phenotype highly variable (pqac-00000009, pqac-00000018, pqac-00000022) |
| USP53-related cholestasis *(newer nomenclature varies)* | **USP53** / USP53 | Tight-junction–associated defect; protein colocalizes/interacts with TJP2 pathway (pqac-00000025, pqac-00000026) | Usually **low/normal** (pqac-00000018) | Low-GGT cholestasis identified by exome sequencing; currently a rarer PFIC-like presentation with limited phenotype definition (pqac-00000018, pqac-00000026) | Natural history and treatment-response data remain sparse (pqac-00000018, pqac-00000026) |
| KIF12-related cholestasis *(sometimes mapped to a later-numbered PFIC; nomenclature varies)* | **KIF12** / kinesin family member 12 | Intracellular trafficking / motor-protein defect affecting hepatocellular bile transport pathways (pqac-00000026, pqac-00000027) | Often reported in the **low/normal-GGT PFIC-like** spectrum, but source conventions vary (pqac-00000026) | Pediatric cholestatic liver disease; detailed extrahepatic pattern remains less established than classical PFIC forms (pqac-00000026) | Evidence base is emerging; numbering and disease boundaries vary across reviews and databases (pqac-00000026) |
| ZFYVE19-related cholestasis *(newer/related PFIC-like gene; numbering varies)* | **ZFYVE19** / zinc finger FYVE-type containing 19 | Ciliary / trafficking-related mechanism proposed in PFIC-like cholestasis; evidence base remains limited in the retrieved sources (pqac-00000000) | Not firmly established here | Reported as a newer PFIC-related gene in expanded molecular classifications, but detailed phenotype data were not available in the retrieved evidence set (pqac-00000000) | Important emerging gene; requires confirmation from primary case literature in a full database curation workflow (pqac-00000000) |
| SLC51A-related cholestasis / OSTα deficiency *(newer/related PFIC-like form; numbering varies)* | **SLC51A** / OSTα | Defect in basolateral bile-acid transport (organic solute transporter α), disturbing enterohepatic bile-acid handling (pqac-00000026) | Often grouped with **low/normal-GGT** PFIC-like disorders, but conventions vary (pqac-00000026) | Early-onset cholestatic phenotype in expanded classifications; detailed syndrome boundaries were not fully captured in the retrieved sources (pqac-00000026) | Limited outcome and treatment-response data in current retrieved evidence (pqac-00000026) |
| VPS33B / VIPAS39-related cholestasis (ARC spectrum; PFIC-like, not always numbered as PFIC) | **VPS33B** / VPS33B; **VIPAS39** / VIPAR | Vesicular trafficking / apical membrane biogenesis defect causing multisystem cholestasis syndrome (pqac-00000018, pqac-00000026) | Often **low/normal** in ARC-associated cholestasis, though syndrome-based classification is preferred (pqac-00000018, pqac-00000026) | Neonatal/infantile cholestasis with multisystem clues: arthrogryposis, renal tubular dysfunction, developmental issues; histology may show bile duct paucity, giant cells, bile plugs (pqac-00000018) | Usually severe syndromic disease; better viewed as a PFIC-like cholestatic disorder rather than classical isolated PFIC (pqac-00000018, pqac-00000026) |
| **Nomenclature note for newer forms** | — | Expanded PFIC numbering beyond PFIC1-5 is **not standardized across sources**; some reviews now include many later-numbered forms, whereas others prefer “PFIC-like” or gene-specific cholestasis terminology (pqac-00000010, pqac-00000012, pqac-00000026) | — | Gene-first reporting is often clearer than subtype numbering for USP53, KIF12, ZFYVE19, SLC51A, and VPS33B/VIPAS39 (pqac-00000010, pqac-00000012, pqac-00000026) | Use explicit gene/protein names in knowledge-base entries to avoid cross-source ambiguity (pqac-00000010, pqac-00000012, pqac-00000026) |


*Table: This table summarizes major classical and newer PFIC-associated genotypes, their core molecular defects, expected GGT patterns, hallmark phenotypes, and key prognostic or treatment-response notes. It is useful for rapid subtype comparison and highlights that nomenclature for newer numbered forms is not standardized across sources.*