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P3H4

gene
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Also known as SC65NO55

Summary

P3H4 (prolyl 3-hydroxylase family member 4 (inactive), HGNC:16946) is a protein-coding gene on chromosome 17q21.2, encoding Endoplasmic reticulum protein SC65 (Q92791). Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils.

This nucleolar protein was first characterized because it was an autoantigen in cases on interstitial cystitis. The protein, with a predicted molecular weight of 50 kDa, appears to be localized in the particulate compartment of the interphase nucleolus, with a distribution distinct from that of nucleolar protein B23. During mitosis it is associated with chromosomes.

Source: NCBI Gene 10609 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 75 total
  • MANE Select transcript: NM_006455

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:16946
Approved symbolP3H4
Nameprolyl 3-hydroxylase family member 4 (inactive)
Location17q21.2
Locus typegene with protein product
StatusApproved
AliasesSC65, NO55
Ensembl geneENSG00000141696
Ensembl biotypeprotein_coding
OMIM617419
Entrez10609

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000355468, ENST00000393928, ENST00000465097, ENST00000467164, ENST00000484247, ENST00000587455, ENST00000590496, ENST00000592026, ENST00000891166, ENST00000914260, ENST00000914261, ENST00000914262, ENST00000914263, ENST00000914264, ENST00000914265, ENST00000970400, ENST00000970401, ENST00000970402

RefSeq mRNA: 1 — MANE Select: NM_006455 NM_006455

CCDS: CCDS11408

Canonical transcript exons

ENST00000393928 — 8 exons

ExonStartEnd
ENSE000025359924181145441811949
ENSE000034812764181113241811284
ENSE000034822944180195341802979
ENSE000036589334180328741803431
ENSE000038898194180785941808004
ENSE000038937604181086341811034
ENSE000038956064180679641806879
ENSE000038958034180970641809834

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 96.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3923 / max 102.3141, expressed in 1572 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
16604713.80211569
1660490.5902393

Top tissues by expression

271 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
stromal cell of endometriumCL:000225596.08gold quality
periodontal ligamentUBERON:000826689.12gold quality
tibiaUBERON:000097988.17gold quality
ventricular zoneUBERON:000305387.21gold quality
adenohypophysisUBERON:000219685.74gold quality
pituitary glandUBERON:000000785.44gold quality
right lobe of thyroid glandUBERON:000111985.30gold quality
left adrenal gland cortexUBERON:003582585.13gold quality
left adrenal glandUBERON:000123485.03gold quality
tendon of biceps brachiiUBERON:000818884.94silver quality
right adrenal glandUBERON:000123384.68gold quality
body of pancreasUBERON:000115084.66gold quality
ascending aortaUBERON:000149684.44gold quality
thoracic aortaUBERON:000151584.31gold quality
adrenal cortexUBERON:000123584.24gold quality
right coronary arteryUBERON:000162584.11gold quality
cartilage tissueUBERON:000241884.11gold quality
endocervixUBERON:000045883.92gold quality
right adrenal gland cortexUBERON:003582783.74gold quality
left lobe of thyroid glandUBERON:000112083.47gold quality
adrenal glandUBERON:000236983.34gold quality
thyroid glandUBERON:000204683.14gold quality
cerebellar hemisphereUBERON:000224583.11gold quality
mucosa of transverse colonUBERON:000499183.08gold quality
cerebellar cortexUBERON:000212983.04gold quality
right hemisphere of cerebellumUBERON:001489082.81gold quality
body of uterusUBERON:000985382.44gold quality
metanephros cortexUBERON:001053382.24gold quality
ectocervixUBERON:001224982.22gold quality
right ovaryUBERON:000211882.16gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes4.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2

miRNA regulators (miRDB)

21 targeting P3H4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3924100.0072.092394
HSA-MIR-4715-3P99.9866.03670
HSA-MIR-6778-3P99.9667.292693
HSA-MIR-3529-3P99.9073.553045
HSA-MIR-3663-3P99.8470.39798
HSA-MIR-3121-3P99.8271.963630
HSA-MIR-182799.6368.573265
HSA-MIR-7159-5P99.5372.122472
HSA-MIR-6878-3P99.2464.23920
HSA-MIR-5584-3P99.2368.791351
HSA-MIR-6504-3P99.1769.312891
HSA-MIR-7151-3P99.0469.722370
HSA-MIR-6506-5P99.0465.661386
HSA-MIR-471098.6165.961048
HSA-MIR-619-5P98.5764.971988
HSA-MIR-5089-5P98.4566.061388
HSA-MIR-4772-3P98.0465.601203
HSA-MIR-66597.6065.641781
HSA-MIR-6869-5P97.1767.06634
HSA-MIR-552-3P96.6864.121026
HSA-MIR-443595.9065.471201

Literature-anchored findings (GeneRIF, showing 5)

  • SC65 protein is identified as an autoimmune target in idiopathic membranous nephropathy. (PMID:23144993)
  • High P3H4 expression is associated with bladder cancer. (PMID:30322400)
  • Knockdown of P3H4 inhibits proliferation and invasion of bladder cancer. (PMID:32018225)
  • P3H4 Overexpression Serves as a Prognostic Factor in Lung Adenocarcinoma. (PMID:34257701)
  • P3H4 and PLOD1 expression associates with poor prognosis in bladder cancer. (PMID:35149972)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriop3h4ENSDARG00000104089
mus_musculusP3h4ENSMUSG00000006931
rattus_norvegicusP3h4ENSRNOG00000015787
caenorhabditis_elegansWBGENE00013531

Paralogs (1): CRTAP (ENSG00000170275)

Protein

Protein identifiers

Endoplasmic reticulum protein SC65 — Q92791 (reviewed: Q92791)

Alternative names: Leprecan-like protein 4, Nucleolar autoantigen No55, Prolyl 3-hydroxylase family member 4, Synaptonemal complex protein SC65

All UniProt accessions (4): H0YED7, K7EJ03, K7ERA3, Q92791

UniProt curated annotations — full annotation on UniProt →

Function. Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. Required for normal bone density and normal skin stability via its role in hydroxylation of lysine residues in collagen alpha chains and in collagen fibril assembly.

Subunit / interactions. Interacts with PLOD1, P3H3 and PPIB. Identified in a complex with PLOD1 and P3H3.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Detected in fibroblasts (at protein level). Detected in spleen, prostate, testis, ovary, colon, pancreas, kidney, placenta and heart.

Similarity. Belongs to the leprecan family.

RefSeq proteins (1): NP_006446* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR011990TPR-like_helical_dom_sfHomologous_superfamily
IPR052284Collagen_mod_leprecanFamily
IPR056585Leprecan_domDomain

Pfam: PF23557

UniProt features (7 total): compositionally biased region 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q92791-F183.750.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 361

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_ORGANELLE_FISSION, MYCMAX_01, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, NERF_Q2, GOBP_PROTEIN_HYDROXYLATION, GOBP_HOMOLOGOUS_CHROMOSOME_PAIRING_AT_MEIOSIS, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, RIZKI_TUMOR_INVASIVENESS_3D_UP

GO Biological Process (5): synaptonemal complex assembly (GO:0007130), peptidyl-lysine hydroxylation (GO:0017185), collagen fibril organization (GO:0030199), collagen biosynthetic process (GO:0032964), bone remodeling (GO:0046849)

GO Molecular Function (2): protein binding (GO:0005515), collagen binding (GO:0005518)

GO Cellular Component (5): condensed nuclear chromosome (GO:0000794), synaptonemal complex (GO:0000795), nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), catalytic complex (GO:1902494)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
homologous chromosome pairing at meiosis1
cellular component assembly1
chromosome organization involved in meiotic cell cycle1
synaptonemal complex organization1
protein hydroxylation1
peptidyl-lysine modification1
extracellular matrix organization1
biosynthetic process1
collagen metabolic process1
tissue remodeling1
binding1
protein-containing complex binding1
nuclear chromosome1
condensed chromosome1
nucleus1
synaptonemal structure1
nuclear lumen1
intracellular membraneless organelle1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
protein-containing complex1

Protein interactions and networks

STRING

528 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
P3H4PPIBP23284818
P3H4PLOD1Q02809738
P3H4FKBP10Q96AY3572
P3H4COLGALT1Q8NBJ5514
P3H4P4HA3Q7Z4N8470
P3H4PLOD3O60568423
P3H4SERPINH1P29043399
P3H4TMEM38BQ9NVV0397
P3H4COL5A2P05997375
P3H4P4HA2O15460357
P3H4COLGALT2Q8IYK4354
P3H4WDR19Q8NEZ3349
P3H4SLC26A2P50443348
P3H4CEP290O15078348
P3H4P4HA1P13674346

IntAct

79 interactions, top by confidence:

ABTypeScore
C1QTNF9C1QTNF9Bpsi-mi:“MI:0914”(association)0.780
CCDC120AIPpsi-mi:“MI:0914”(association)0.640
ZNF397ZNF213psi-mi:“MI:0914”(association)0.640
HRGPLSCR1psi-mi:“MI:0914”(association)0.590
OS9AGRNpsi-mi:“MI:0914”(association)0.530
ALX3CRTAPpsi-mi:“MI:0914”(association)0.530
C1QTNF9BPLOD3psi-mi:“MI:0914”(association)0.530
ADAMTS4MANBApsi-mi:“MI:0914”(association)0.530
CHSY3CHSY1psi-mi:“MI:0914”(association)0.530
PLOD3PLOD2psi-mi:“MI:0914”(association)0.530
TAF1CDNAJA2psi-mi:“MI:0914”(association)0.530
CPSF6DDX39Apsi-mi:“MI:0914”(association)0.480
AGPSpsi-mi:“MI:0915”(physical association)0.400
HSCBRBP5psi-mi:“MI:0914”(association)0.350
ORF27GNPATpsi-mi:“MI:0914”(association)0.350
PLOD1COL25A1psi-mi:“MI:0914”(association)0.350
C1QTNF2GNPATpsi-mi:“MI:0914”(association)0.350
CHST8CLSTN1psi-mi:“MI:0914”(association)0.350
COLQPLOD2psi-mi:“MI:0914”(association)0.350
CHSY3STK17Bpsi-mi:“MI:0914”(association)0.350
COLEC10PTX3psi-mi:“MI:0914”(association)0.350
DENND11psi-mi:“MI:0914”(association)0.350
CANXHLA-Apsi-mi:“MI:0914”(association)0.350
SFTPA2PRPSAP2psi-mi:“MI:0914”(association)0.350
C1QTNF8VWA8psi-mi:“MI:0914”(association)0.350
RLN1RTL8Cpsi-mi:“MI:0914”(association)0.350
PLOD1PLK4psi-mi:“MI:0914”(association)0.350
CHST8CALUpsi-mi:“MI:0914”(association)0.350

BioGRID (94): P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), P3H4 (Affinity Capture-MS)

ESM2 similar proteins: A2ARS0, A6NH11, A6QQ91, C9JTQ0, D3ZVB0, D4A929, G3MZC5, O75064, O95996, P16386, P46062, P58660, Q02011, Q08DF2, Q16619, Q29RK8, Q2TBW5, Q2VPB7, Q3TAP4, Q3U0S6, Q3U1Y4, Q562E7, Q5TA50, Q5U651, Q60753, Q63086, Q64375, Q68J42, Q6P9B9, Q6ZS72, Q86YV0, Q8BH02, Q8BQU6, Q8C2K5, Q8CHT3, Q8K0R6, Q8K2B0, Q8N9M5, Q8VD26, Q92791

Diamond homologs: O75718, Q32P28, Q3V1T4, Q4KLM6, Q64375, Q6JHU7, Q6JHU8, Q8CG71, Q8IVL5, Q8K2B0, Q90830, Q92791, Q9CYD3, Q9R1J8, Q6PK18, Q8CG70, Q8IVL6, Q5M843, Q5XGE0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Collagen biosynthesis and modifying enzymes817.3×6e-06

GO biological processes:

GO termPartnersFoldFDR
collagen fibril organization716.4×8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

75 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance64
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

990 predictions. Top by Δscore:

VariantEffectΔscore
17:41803285:ACCAG:Adonor_gain1.0000
17:41803286:CCAGC:Cdonor_gain1.0000
17:41803449:T:TCacceptor_gain1.0000
17:41806791:CTCA:Cdonor_loss1.0000
17:41806792:TCAC:Tdonor_loss1.0000
17:41806793:CACCT:Cdonor_loss1.0000
17:41806794:A:ACdonor_gain1.0000
17:41806794:AC:Adonor_gain1.0000
17:41806794:ACCT:Adonor_gain1.0000
17:41806795:C:CAdonor_gain1.0000
17:41806795:C:Gdonor_loss1.0000
17:41806795:CC:Cdonor_gain1.0000
17:41806795:CCT:Cdonor_gain1.0000
17:41806795:CCTC:Cdonor_gain1.0000
17:41806795:CCTCA:Cdonor_gain1.0000
17:41806875:GCCTC:Gacceptor_gain1.0000
17:41806876:CCTCC:Cacceptor_gain1.0000
17:41806877:CTC:Cacceptor_gain1.0000
17:41806878:TC:Tacceptor_gain1.0000
17:41806879:CC:Cacceptor_gain1.0000
17:41806880:C:CAacceptor_loss1.0000
17:41806880:C:CCacceptor_gain1.0000
17:41806881:T:Gacceptor_loss1.0000
17:41807854:CCCA:Cdonor_loss1.0000
17:41807855:CCA:Cdonor_loss1.0000
17:41807856:CACC:Cdonor_loss1.0000
17:41807858:C:CGdonor_loss1.0000
17:41807860:T:TAdonor_gain1.0000
17:41807861:C:Adonor_gain1.0000
17:41807875:T:TAdonor_gain1.0000

AlphaMissense

2852 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:41807967:G:CS318R0.999
17:41807967:G:TS318R0.999
17:41807969:T:GS318R0.999
17:41809719:A:CF301L0.999
17:41809719:A:TF301L0.999
17:41809721:A:GF301L0.999
17:41809726:A:GL299P0.999
17:41809798:C:TC275Y0.999
17:41809797:A:CC275W0.998
17:41811689:C:TC76Y0.998
17:41809720:A:CF301C0.997
17:41809798:C:AC275F0.997
17:41809798:C:GC275S0.997
17:41809799:A:GC275R0.997
17:41809799:A:TC275S0.997
17:41810916:C:TC245Y0.997
17:41810981:G:CS223R0.997
17:41810981:G:TS223R0.997
17:41810983:T:GS223R0.997
17:41811500:A:GF139S0.997
17:41811689:C:GC76S0.997
17:41811690:A:TC76S0.997
17:41811760:C:AW52C0.997
17:41811760:C:GW52C0.997
17:41811026:G:CF208L0.996
17:41811026:G:TF208L0.996
17:41811027:A:CF208C0.996
17:41811027:A:GF208S0.996
17:41811028:A:GF208L0.996
17:41811500:A:CF139C0.996

dbSNP variants (sampled 300 via entrez): RS1001731014 (17:41808211 T>C), RS1002053633 (17:41802627 C>T), RS1002288350 (17:41812783 G>A), RS1002778833 (17:41810249 A>C,G), RS1003919189 (17:41813917 C>T), RS1004965490 (17:41808149 G>A), RS1004994006 (17:41802035 C>T), RS1005282793 (17:41802365 C>T), RS1005520682 (17:41805387 C>T), RS1005578712 (17:41807799 C>A), RS1005677985 (17:41804950 G>A), RS1005882099 (17:41803698 C>G,T), RS1006174019 (17:41809546 G>A), RS1006530557 (17:41806704 G>A), RS1006814689 (17:41811991 C>A,G)

Disease associations

OMIM: gene MIM:617419 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST002279_98PR interval in Tripanosoma cruzi seropositivity3.000000e-08
GCST007269_303Pulse pressure7.000000e-09

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0004462PR interval
EFO:0005763pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, increases methylation5
bisphenol Adecreases expression, increases expression2
sodium arsenitedecreases expression2
perfluorooctanoic aciddecreases expression2
Tobacco Smoke Pollutionaffects expression, decreases expression2
Aflatoxin B1decreases expression, increases methylation2
Particulate Matterdecreases expression, increases abundance, increases expression2
testosterone enanthateaffects expression1
triphenyl phosphateaffects expression1
cobaltous chloridedecreases expression1
aflatoxin B2decreases methylation1
cupric chlorideaffects expression1
beta-methylcholineaffects expression1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic acidincreases expression1
abrinedecreases expression1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
bisphenol AFincreases expression1
Temozolomideincreases expression1
Air Pollutantsdecreases expression, increases abundance1
Vehicle Emissionsincreases abundance, increases expression1
Benzo(a)pyreneaffects methylation1
Copperaffects binding, increases expression1
Diethylhexyl Phthalatedecreases expression1
Disulfiramaffects binding, increases expression1
Hydrogen Peroxideaffects expression1
Ivermectindecreases expression1
Plant Oilsdecreases expression1
Smokedecreases expression1
Thiramdecreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot