PATJ

Summary

PATJ (PATJ crumbs cell polarity complex component, HGNC:28881) is a protein-coding gene on chromosome 1p31.3, encoding InaD-like protein (Q8NI35). Scaffolding protein that facilitates the localization of proteins to the cell membrane.

This gene encodes a protein with multiple PDZ domains. PDZ domains mediate protein-protein interactions, and proteins with multiple PDZ domains often organize multimeric complexes at the plasma membrane. This protein localizes to tight junctions and to the apical membrane of epithelial cells. A similar protein in Drosophila is a scaffolding protein which tethers several members of a multimeric signaling complex in photoreceptors.

Source: NCBI Gene 10207 — RefSeq curated summary.

At a glance

• GWAS associations: 34
• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_001350145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28881
Approved symbol	PATJ
Name	PATJ crumbs cell polarity complex component
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	Cipp
Ensembl gene	ENSG00000132849
Ensembl biotype	protein_coding
OMIM	603199
Entrez	10207

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000307297, ENST00000371158, ENST00000459752, ENST00000465798, ENST00000472512, ENST00000484562, ENST00000484937, ENST00000488913, ENST00000490547, ENST00000493967, ENST00000494842, ENST00000635023, ENST00000635137, ENST00000635214, ENST00000642238, ENST00000646453

RefSeq mRNA: 2 — MANE Select: NM_001350145 NM_001350145, NM_176877

CCDS: CCDS617, CCDS85980

Canonical transcript exons

ENST00000642238 — 44 exons

Exon	Start	End
ENSE00001639463	62117132	62117218
ENSE00001668046	62121181	62121295
ENSE00002685573	62114053	62114246
ENSE00003460325	62017856	62017947
ENSE00003488004	61899583	61899654
ENSE00003492212	61861551	61861667
ENSE00003493409	62037977	62038049
ENSE00003501436	62079450	62079567
ENSE00003509881	62148284	62148390
ENSE00003513784	61822945	61823079
ENSE00003521079	61775206	61775334
ENSE00003522923	61914587	61914664
ENSE00003532448	61795467	61795558
ENSE00003544558	61875243	61875366
ENSE00003548958	61771431	61771626
ENSE00003551431	61762858	61762914
ENSE00003571618	62050966	62051058
ENSE00003578001	61927730	61927829
ENSE00003580776	61801623	61801769
ENSE00003589240	61908372	61908482
ENSE00003595071	62128841	62128945
ENSE00003596843	61884237	61884408
ENSE00003599889	62084515	62084648
ENSE00003605583	61791348	61791447
ENSE00003612860	61833654	61833785
ENSE00003617026	61864238	61864633
ENSE00003617420	61763013	61763179
ENSE00003643420	61856030	61856239
ENSE00003646545	61787754	61787972
ENSE00003661259	61990168	61990364
ENSE00003665649	61769283	61769422
ENSE00003671298	62116532	62116679
ENSE00003676555	61805448	61805524
ENSE00003682288	62123021	62123058
ENSE00003682387	61901282	61901459
ENSE00003685742	61797287	61797428
ENSE00003685850	61766279	61766473
ENSE00003688666	61808474	61808530
ENSE00003689257	62108437	62108520
ENSE00003694004	62127972	62128094
ENSE00003694245	61827422	61827583
ENSE00003814897	61742480	61742555
ENSE00003821567	62153358	62153481
ENSE00003900740	62160908	62163915

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8278 / max 421.0428, expressed in 1171 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3110	9.8836	1108
3121	0.3992	92
3123	0.2931	55
3109	0.2835	136
3118	0.2773	68
3122	0.2761	72
3108	0.2276	122
3119	0.1100	37
3117	0.0435	20
3127	0.0260	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	96.66	gold quality
lower esophagus mucosa	UBERON:0035834	94.95	gold quality
renal medulla	UBERON:0000362	94.71	gold quality
pons	UBERON:0000988	94.50	gold quality
cerebellar cortex	UBERON:0002129	94.36	gold quality
cerebellar hemisphere	UBERON:0002245	94.34	gold quality
cerebellum	UBERON:0002037	93.93	gold quality
calcaneal tendon	UBERON:0003701	93.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.42	gold quality
gingival epithelium	UBERON:0001949	91.74	gold quality
cerebellar vermis	UBERON:0004720	91.59	gold quality
cardiac ventricle	UBERON:0002082	91.55	gold quality
corpus epididymis	UBERON:0004359	91.53	gold quality
heart left ventricle	UBERON:0002084	91.40	gold quality
gingiva	UBERON:0001828	91.34	gold quality
apex of heart	UBERON:0002098	91.32	gold quality
minor salivary gland	UBERON:0001830	90.91	gold quality
germinal epithelium of ovary	UBERON:0001304	90.80	gold quality
mouth mucosa	UBERON:0003729	90.73	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.72	gold quality
biceps brachii	UBERON:0001507	90.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.28	gold quality
oral cavity	UBERON:0000167	90.25	gold quality
colonic mucosa	UBERON:0000317	90.24	gold quality
esophagus mucosa	UBERON:0002469	90.13	gold quality
esophagus squamous epithelium	UBERON:0006920	89.66	gold quality
bronchial epithelial cell	CL:0002328	89.63	gold quality
skin of abdomen	UBERON:0001416	89.55	gold quality
seminal vesicle	UBERON:0000998	89.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.16
E-MTAB-11268	no	795.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

Literature-anchored findings (GeneRIF, showing 11)

• interaction with crumbs and localization to tight junctions in epithelial cells (PMID:11964389)
• Data show that PATJ regulates the spatial concentration of several tight junction components at the border between the apical and lateral domains in Caco-2 cells. (PMID:16129888)
• PATJ controls directional migration by regulating the localization of aPKC and Par3 to the leading edge of epithelial cells. (PMID:17235357)
• We have identified the tight junction-associated multi-PDZ protein PATJ (PALS1-associated TJ protein) as a novel binding partner and degradation target of high-risk types 16 and 18 E6. (PMID:17287269)
• the directional migration of capillaries in the embryo is governed by the Amot:Patj/Mupp1:Syx signaling that controls local GTPase activity (PMID:18824598)
• Data show taht channel-interacting PDZ protein, ‘CIPP’, interacts with proteins involved in cytoskeletal dynamics. (PMID:19138174)
• Results suggest that signaling mediated by Pals1, which has a higher affinity for Patj than for MUPP1 and is involved in the activation of the Par6-aPKC complex, is of principal importance for the function of Patj in epithelial cells. (PMID:19255144)
• Signalling molecules and effectors can be integrated into a functional network by the scaffold organizer protein PATJ via its multiple PDZ domains. (PMID:19563532)
• Results indicate a role for Yes associated protein (YAP), which is inhibited by the Hippo pathway, in the cytokinesis machinery during mitosis through interaction with the polarity protein PATJ. (PMID:26933062)
• Meta-analysis: Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 . (PMID:30582445)
• MUC1 and Polarity Markers INADL and SCRIB Identify Salivary Ductal Cells. (PMID:35259994)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	patj	ENSDARG00000024964
mus_musculus	Patj	ENSMUSG00000061859
rattus_norvegicus	Patj	ENSRNOG00000007551
drosophila_melanogaster	Patj	FBGN0067864
caenorhabditis_elegans		WBGENE00001492
caenorhabditis_elegans		WBGENE00003404
caenorhabditis_elegans		WBGENE00021406

Paralogs (5): LNX1 (ENSG00000072201), MPDZ (ENSG00000107186), LNX2 (ENSG00000139517), STXBP4 (ENSG00000166263), FRMPD2 (ENSG00000170324)

Protein

Protein identifiers

InaD-like protein — Q8NI35 (reviewed: Q8NI35)

Alternative names: Channel-interacting PDZ domain-containing protein, Pals1-associated tight junction protein, Protein associated to tight junctions

All UniProt accessions (9): A0A0U1RQR3, Q8NI35, A0A0U1RQT2, A0A0U1RQW4, A0A0U1RR46, A0A0U1RRD7, A0A2R8Y549, A0A2R8Y5I3, B4DE90

UniProt curated annotations — full annotation on UniProt →

Function. Scaffolding protein that facilitates the localization of proteins to the cell membrane. Required for the correct formation of tight junctions and epithelial apico-basal polarity. Acts (via its L27 domain) as an apical connector and elongation factor for multistranded TJP1/ZO1 condensates that form a tight junction belt, thereby required for the formation of the tight junction-mediated cell barrier. Positively regulates epithelial cell microtubule elongation and cell migration, possibly via facilitating localization of PRKCI/aPKC and PAR3D/PAR3 at the leading edge of migrating cells. Plays a role in the correct reorientation of the microtubule-organizing center during epithelial migration. May regulate the surface expression and/or function of ASIC3 in sensory neurons. May recruit ARHGEF18 to apical cell-cell boundaries.

Subunit / interactions. Forms a ternary complex with PALS1, CRB1 and CRB3. Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, INADL/PATJ and PARD3/PAR3. Forms a heterotrimeric complex composed of MMP5, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B. Component of a complex composed of CRB3, PALS1 and PATJ. Interacts (via N-terminus) with PALS1/PALS (via PDZ domain). As part of the Crumbs complex; interacts with WWP1, the interaction is enhanced by AMOTL2 and facilitates WWP1 localization to the plasma membrane. The Crumbs complex promotes monoubiquitination of AMOTL2 by WWP1, which activates the Hippo signaling pathway. Interacts with TJP3/ZO-3 and CLDN1/claudin-1. Interacts with ASIC3, KCNJ10, KCNJ15, GRIN2A, GRIN2B, GRIN2C, GRIN2D, NLGN2, HTR2A and SLC6A4. Interacts with MPP7. Directly interacts with HTR4. Interacts (via PDZ domain 8) with WWC1 (via the ADDV motif). Interacts with SLC6A4. Interacts (via C-terminus) with ARHGEF18. Interacts with NPHP1. Interacts with PARD3/PAR3. Interacts (via PDZ1-6 domains) with TJP1/ZO1; the interaction is required for attachment and extension of TJP1/ZO1 condensates along the apical cell interface.

Subcellular location. Cell junction. Tight junction. Apical cell membrane. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in renal tubules (at protein level). Expressed in bladder, testis, ovary, small intestine, colon, heart, skeletal muscle, pancreas and cerebellum in the brain.

Domain organisation. The L27 domain (also called Maguk recruitment domain) is required for interaction with PALS1 and CRB3, and PALS1 localization to tight junctions. The PDZ domain 6 mediates interaction with the C-terminus of TJP3 and is crucial for localization to the tight junctions. The PDZ domain 8 interacts with CLDN1 but is not required for proper localization.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NI35-1	1	yes
Q8NI35-2	2
Q8NI35-3	3
Q8NI35-4	4
Q8NI35-5	5

RefSeq proteins (2): NP_001337074, NP_795352 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR004172	L27_dom	Domain
IPR015132	L27_2	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR036892	L27_dom_sf	Homologous_superfamily
IPR051342	PDZ_scaffold	Family

Pfam: PF00595, PF09045

UniProt features (126 total): strand 52, helix 22, sequence variant 12, domain 11, modified residue 7, splice variant 6, region of interest 5, compositionally biased region 5, mutagenesis site 2, sequence conflict 2, chain 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4Q2N	X-RAY DIFFRACTION	2
1VF6	X-RAY DIFFRACTION	2.1
6IRD	X-RAY DIFFRACTION	2.81
2D92	SOLUTION NMR
2DAZ	SOLUTION NMR
2DB5	SOLUTION NMR
2DLU	SOLUTION NMR
2DM8	SOLUTION NMR
2DMZ	SOLUTION NMR
2EHR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI35-F1	60.87	0.09

Functional residue map

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

Post-translational modifications (7): 455, 459, 522, 645, 1209, 1212, 1508

Mutagenesis-validated functional residues (2):

Position	Phenotype
19	reduces l27 domain binding affinity to pals1 l27 domain.
38	reduces l27 domain binding affinity to pals1 l27 domain.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions
R-HSA-9705677	SARS-CoV-2 targets PDZ proteins in cell-cell junction
R-HSA-1500931	Cell-Cell communication
R-HSA-1643685	Disease
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 223 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOZGIT_ESR1_TARGETS_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, KEGG_TIGHT_JUNCTION, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_CELL_JUNCTION_ORGANIZATION, GROSS_HYPOXIA_VIA_ELK3_UP, GOCC_CENTROSOME, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (4): establishment of apical/basal cell polarity (GO:0035089), intracellular signal transduction (GO:0035556), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), tight junction assembly (GO:0120192)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), apical plasma membrane (GO:0016324), cell junction (GO:0030054), centriolar satellite (GO:0034451), apical junction complex (GO:0043296), apical part of cell (GO:0045177), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), membrane (GO:0016020), tight junction (GO:0070160), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Cell-cell junction organization	1
SARS-CoV-2-host interactions	1
Cell junction organization	1
Cell-Cell communication	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
establishment or maintenance of apical/basal cell polarity	2
intracellular anatomical structure	2
cytoplasm	2
cell-cell junction	2
establishment of monopolar cell polarity	1
signal transduction	1
cell-cell junction assembly	1
tight junction organization	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
apical part of cell	1
plasma membrane region	1
centrosome	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PATJ	PALS1	Q8N3R9	999
PATJ	CRB3	Q9BUF7	998
PATJ	AMOT	Q4VCS5	998
PATJ	CRB2	Q5IJ48	995
PATJ	CRB1	P82279	993
PATJ	ARHGAP17	Q68EM7	969
PATJ	LIN7A	O14910	962
PATJ	TJP3	O95049	952
PATJ	CLDN1	O95832	951
PATJ	CLDN7	O95471	899
PATJ	TJP1	Q07157	852
PATJ	MPDZ	O75970	848
PATJ	OCLN	Q16625	830
PATJ	PARD6A	Q9NPB6	814
PATJ	JAM3	Q9BX67	812

IntAct

3547 interactions, top by confidence:

A	B	Type	Score
PALS1	LIN7A	psi-mi:“MI:0914”(association)	0.870
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YAP1	PATJ	psi-mi:“MI:0407”(direct interaction)	0.710
PATJ	YAP1	psi-mi:“MI:0407”(direct interaction)	0.710
TJP3	PATJ	psi-mi:“MI:0407”(direct interaction)	0.680
PATJ	TANC1	psi-mi:“MI:0407”(direct interaction)	0.620
PATJ	PKP4	psi-mi:“MI:0407”(direct interaction)	0.620
E	PATJ	psi-mi:“MI:0915”(physical association)	0.610
PATJ	PRKCA	psi-mi:“MI:0407”(direct interaction)	0.550
PTEN	PATJ	psi-mi:“MI:0407”(direct interaction)	0.540
PTEN	PATJ	psi-mi:“MI:0915”(physical association)	0.540
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
LIN7C	ABLIM1	psi-mi:“MI:0914”(association)	0.530
LIN7B	CASK	psi-mi:“MI:0914”(association)	0.530
RNF166	MPDZ	psi-mi:“MI:0914”(association)	0.530
PALS1	AMOTL1	psi-mi:“MI:0914”(association)	0.530
NF2	AMOT	psi-mi:“MI:0914”(association)	0.500
NF2	PATJ	psi-mi:“MI:0915”(physical association)	0.500
E6	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
NRXN3	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
PATJ	NRXN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (144): INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS), INADL (Affinity Capture-MS)

ESM2 similar proteins: B2GUY1, E2QYC9, E7F1U2, E7FDW2, E9Q9W7, F1MAD2, O15018, O54960, O55164, O75970, P68907, Q12923, Q13009, Q4L1J4, Q5RBI7, Q60610, Q63ZW7, Q64512, Q69ZS0, Q6AWC2, Q6DJR2, Q6IVY4, Q6RHR9, Q6XZF7, Q6ZMN7, Q80VW5, Q810W9, Q8N680, Q8NI35, Q8TEW0, Q8VBX6, Q92870, Q96QZ7, Q99N50, Q99NH2, Q9BYG5, Q9D3A8, Q9DBR4, Q9DDT2, Q9EQZ7

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, B4F7E7, D3ZAA9, E2QY99, E2QYC9, E7FDW2, F1MAD2, G5ECY0, O14910, O15018, O55164, O75970, O84033, O88382, O88951, O88952, P15454, P31006, P31007, P31016, P46195, P57105, P68907, P70175, P78352, P93757, Q0P5F3, Q0SS73, Q0TPK6, Q12959, Q13425, Q13884, Q14160, Q15700, Q16774, Q24210, Q255A8, Q28C55, Q2KIB6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PATJ	“form complex”	AMOT/MPP5/INADL/LIN7C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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:

Pathway	Partners	Fold	FDR
Signaling by Hippo	6	25.9×	2e-05
Dopamine Neurotransmitter Release Cycle	5	19.7×	9e-04
Neurexins and neuroligins	10	15.6×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	7	32.7×	2e-06
adult behavior	5	14.9×	4e-03
learning	6	10.7×	4e-03
social behavior	6	10.4×	4e-03
synapse assembly	6	8.8×	7e-03
transmembrane transport	7	7.5×	5e-03
angiogenesis	11	4.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	5
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

9441 predictions. Top by Δscore:

Variant	Effect	Δscore
1:61763010:A:AG	acceptor_gain	1.0000
1:61763011:A:G	acceptor_gain	1.0000
1:61763175:GTCAA:G	donor_gain	1.0000
1:61763176:TC:T	donor_gain	1.0000
1:61763176:TCAA:T	donor_gain	1.0000
1:61763177:CAAGT:C	donor_loss	1.0000
1:61763178:AAG:A	donor_loss	1.0000
1:61763179:AGT:A	donor_loss	1.0000
1:61763180:G:GG	donor_gain	1.0000
1:61763181:TAA:T	donor_loss	1.0000
1:61766277:A:AG	acceptor_gain	1.0000
1:61766278:G:GG	acceptor_gain	1.0000
1:61766469:CTCAG:C	donor_loss	1.0000
1:61766470:TCAG:T	donor_loss	1.0000
1:61766471:CAGGT:C	donor_loss	1.0000
1:61766474:G:GC	donor_loss	1.0000
1:61766475:T:A	donor_loss	1.0000
1:61769281:A:AG	acceptor_gain	1.0000
1:61769281:AG:A	acceptor_gain	1.0000
1:61769282:G:GG	acceptor_gain	1.0000
1:61769282:GG:G	acceptor_gain	1.0000
1:61769407:G:GT	donor_gain	1.0000
1:61769418:GACAG:G	donor_gain	1.0000
1:61769420:CAGGT:C	donor_loss	1.0000
1:61769422:GGT:G	donor_loss	1.0000
1:61769423:G:GC	donor_loss	1.0000
1:61769424:T:A	donor_loss	1.0000
1:61769428:G:GT	donor_gain	1.0000
1:61771423:T:G	acceptor_gain	1.0000
1:61775330:ATCGA:A	donor_gain	1.0000

AlphaMissense

12293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:61775264:T:C	F260S	1.000
1:61908457:T:A	V1156D	1.000
1:61775237:T:C	L251P	0.999
1:61775263:T:C	F260L	0.999
1:61775265:T:A	F260L	0.999
1:61775265:T:G	F260L	0.999
1:61775270:T:A	I262K	0.999
1:61787782:T:A	I293N	0.999
1:61787782:T:C	I293T	0.999
1:61787782:T:G	I293S	0.999
1:61787842:T:C	L313P	0.999
1:61787863:T:A	V320D	0.999
1:61833711:T:A	W680R	0.999
1:61833711:T:C	W680R	0.999
1:61833766:T:C	F698S	0.999
1:61899638:T:A	W1063R	0.999
1:61899638:T:C	W1063R	0.999
1:61899640:G:C	W1063C	0.999
1:61899640:G:T	W1063C	0.999
1:61901316:G:A	G1080R	0.999
1:61901316:G:C	G1080R	0.999
1:61901316:G:T	G1080W	0.999
1:61901326:T:A	I1083N	0.999
1:61901385:T:C	F1103L	0.999
1:61901386:T:C	F1103S	0.999
1:61901387:C:A	F1103L	0.999
1:61901387:C:G	F1103L	0.999
1:61901389:T:A	I1104N	0.999
1:61901434:T:A	L1119H	0.999
1:61901434:T:C	L1119P	0.999

dbSNP variants (sampled 300 via entrez): RS1000002427 (1:61814317 T>A), RS1000021387 (1:62152626 G>C), RS1000030010 (1:62077410 G>A,T), RS1000046032 (1:61844152 G>A), RS1000051270 (1:61927221 T>C), RS1000052943 (1:61851643 G>A), RS1000060513 (1:62017537 C>A,G), RS1000063851 (1:62070952 C>T), RS1000068448 (1:62055914 A>C), RS1000070132 (1:61916941 G>A), RS1000080579 (1:61939930 T>G), RS1000093242 (1:61975515 A>G), RS1000100064 (1:61851326 A>T), RS1000102196 (1:61983451 A>G), RS1000127718 (1:61927076 C>A)

Disease associations

OMIM: gene MIM:603199 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST001762_267	Obesity-related traits	7.000000e-06
GCST001762_380	Obesity-related traits	8.000000e-06
GCST001762_402	Obesity-related traits	2.000000e-07
GCST001762_461	Obesity-related traits	7.000000e-06
GCST001762_616	Obesity-related traits	3.000000e-07
GCST001762_623	Obesity-related traits	2.000000e-07
GCST001762_633	Obesity-related traits	3.000000e-06
GCST001762_662	Obesity-related traits	1.000000e-07
GCST001762_682	Obesity-related traits	6.000000e-06
GCST001762_896	Obesity-related traits	7.000000e-06
GCST001762_90	Obesity-related traits	3.000000e-07
GCST002783_179	Body mass index	2.000000e-07
GCST002783_283	Body mass index	6.000000e-07
GCST002783_585	Body mass index	7.000000e-06
GCST003837_12	Chronotype	3.000000e-08
GCST003838_11	Morning vs. evening chronotype	4.000000e-06
GCST003979_12	Excessive daytime sleepiness	7.000000e-07
GCST003982_1	Sleep traits (multi-trait analysis)	1.000000e-10
GCST004136_33	Methadone dose in opioid dependence	7.000000e-06
GCST004495_114	BMI (adjusted for smoking behaviour)	3.000000e-11
GCST004497_111	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-08
GCST004499_44	BMI in non-smokers	4.000000e-08
GCST006920_5	Regular attendance at a gym or sports club	1.000000e-08
GCST006935_1	3-month functional outcome in ischaemic stroke (modified Rankin score)	2.000000e-09
GCST007008_2	Cerebrospinal fluid p-tau levels	7.000000e-07
GCST007393_3	Mitochondrial DNA copy number	8.000000e-07
GCST007565_157	Morning person	7.000000e-19
GCST007576_8	Chronotype	7.000000e-19
GCST009379_28	Type 2 diabetes	1.000000e-08
GCST010584_2	Autism spectrum disorders (social interaction)	4.000000e-08

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0005000	leptin measurement
EFO:0004340	body mass index
EFO:0005106	body composition measurement
EFO:0005109	energy expenditure
EFO:0004338	body weight
EFO:0004995	lean body mass
EFO:0007875	excessive daytime sleepiness measurement
EFO:0007876	insomnia measurement
EFO:0007907	methadone dose measurement
EFO:0004318	smoking behavior
EFO:0009592	social interaction measurement
EFO:0009603	stroke outcome severity measurement
EFO:0004763	p-tau measurement
EFO:0006312	mitochondrial DNA measurement
EFO:0008328	chronotype measurement
EFO:0005426	autism spectrum disorder symptom
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	7
Acetaminophen	decreases expression, increases expression	4
Valproic Acid	affects cotreatment, increases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
dibenzo(a,l)pyrene	decreases expression	1
pentanal	decreases expression	1
corosolic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Panobinostat	affects cotreatment, increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1

Clinical trials (associated diseases)

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