PRR3

Summary

PRR3 (proline rich 3, HGNC:21149) is a protein-coding gene on chromosome 6p21.33, encoding Proline-rich protein 3 (P79522).

Enables RNA binding activity. Predicted to be involved in positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled. Predicted to be part of PTW/PP1 phosphatase complex. Predicted to be active in chromatin.

Source: NCBI Gene 80742 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 39 total
• GTEx eGene: eQTL in 3 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.96 (unconstrained)
• MANE Select transcript: NM_025263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21149
Approved symbol	PRR3
Name	proline rich 3
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	CAT56, Em:AB014077.1, Em:AB023052.2
Ensembl gene	ENSG00000204576
Ensembl biotype	protein_coding
Entrez	80742

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000376560

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 2

ENST00000376560, ENST00000376557, ENST00000470703, ENST00000481741, ENST00000491173, ENST00000498336, ENST00000934408, ENST00000998631, ENST00000998632, ENST00001141554

RefSeq mRNA: 2 — MANE Select: NM_025263 NM_001077497, NM_025263

CCDS: CCDS43440, CCDS43441

Canonical transcript exons

ENST00000376560 — 4 exons

Exon	Start	End
ENSE00001876281	30557295	30557450
ENSE00003578614	30561834	30562124
ENSE00003671319	30558150	30558212
ENSE00003901246	30562389	30563723

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.0091 / max 224.3093, expressed in 1808 samples.

Highest expression (Bgee): cortical plate, ganglionic eminence, cerebellar hemisphere, cerebellar cortex, cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRR3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.2e-04	+0.62	6:30385830:T:C
Adipose Visceral Omentum	sqtl	6.9e-04	-1.14	6:29980810:C:CA
Cells Cultured fibroblasts	sqtl	2.6e-02	+0.95	6:31539383:A:G
Brain Frontal Cortex BA9	eqtl	4.9e-02	+0.37	6:30406108:C:T
Liver	eqtl	5.0e-02	+0.63	6:30698611:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
66737	19.4776	1793
66734	1.8485	893
66736	1.7004	953
66735	0.8888	369
66733	0.7072	340
66739	0.2985	137
66732	0.0883	34

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.54	gold quality
ganglionic eminence	UBERON:0004023	92.30	gold quality
cerebellar hemisphere	UBERON:0002245	89.80	gold quality
cerebellar cortex	UBERON:0002129	89.76	gold quality
cerebellum	UBERON:0002037	89.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.60	gold quality
left ovary	UBERON:0002119	88.95	gold quality
ovary	UBERON:0000992	88.84	gold quality
right ovary	UBERON:0002118	88.40	gold quality
ventricular zone	UBERON:0003053	88.15	gold quality
superior frontal gyrus	UBERON:0002661	87.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.10	gold quality
endocervix	UBERON:0000458	87.07	gold quality
pituitary gland	UBERON:0000007	86.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.69	gold quality
adenohypophysis	UBERON:0002196	86.57	gold quality
body of uterus	UBERON:0009853	86.56	gold quality
hypothalamus	UBERON:0001898	86.42	gold quality
primary visual cortex	UBERON:0002436	86.28	gold quality
right frontal lobe	UBERON:0002810	86.25	gold quality
anterior cingulate cortex	UBERON:0009835	86.08	gold quality
endometrium	UBERON:0001295	85.99	gold quality
nucleus accumbens	UBERON:0001882	85.89	gold quality
caudate nucleus	UBERON:0001873	85.67	gold quality
lymph node	UBERON:0000029	85.63	gold quality
fallopian tube	UBERON:0003889	85.33	gold quality
putamen	UBERON:0001874	85.31	gold quality
uterine cervix	UBERON:0000002	85.30	gold quality
brain	UBERON:0000955	85.29	gold quality
Ammon’s horn	UBERON:0001954	85.25	gold quality
granulocyte	CL:0000094	85.21	gold quality
ectocervix	UBERON:0012249	85.18	gold quality
right uterine tube	UBERON:0001302	85.14	gold quality
right lobe of thyroid gland	UBERON:0001119	84.88	gold quality
myometrium	UBERON:0001296	84.87	gold quality
skin of leg	UBERON:0001511	84.77	gold quality
thyroid gland	UBERON:0002046	84.65	gold quality
left lobe of thyroid gland	UBERON:0001120	84.61	gold quality
tibial nerve	UBERON:0001323	84.60	gold quality
left uterine tube	UBERON:0001303	84.51	gold quality
amygdala	UBERON:0001876	84.43	gold quality
temporal lobe	UBERON:0001871	84.34	gold quality
left adrenal gland cortex	UBERON:0035825	84.34	gold quality
right adrenal gland	UBERON:0001233	84.29	gold quality
prostate gland	UBERON:0002367	84.25	gold quality
zone of skin	UBERON:0000014	84.14	gold quality
right adrenal gland cortex	UBERON:0035827	84.04	gold quality
spleen	UBERON:0002106	83.95	gold quality
left adrenal gland	UBERON:0001234	83.84	gold quality
cerebral cortex	UBERON:0000956	83.75	gold quality
metanephros cortex	UBERON:0010533	83.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.62	gold quality
adrenal gland	UBERON:0002369	83.54	gold quality
vagina	UBERON:0000996	83.50	gold quality
thoracic mammary gland	UBERON:0005200	83.45	gold quality
skin of abdomen	UBERON:0001416	83.44	gold quality
smooth muscle tissue	UBERON:0001135	83.41	gold quality
calcaneal tendon	UBERON:0003701	83.34	gold quality
cortex of kidney	UBERON:0001225	83.23	gold quality
adipose tissue	UBERON:0001013	82.88	gold quality
right lobe of liver	UBERON:0001114	82.73	gold quality
descending thoracic aorta	UBERON:0002345	82.65	gold quality
vermiform appendix	UBERON:0001154	82.64	gold quality
body of pancreas	UBERON:0001150	82.63	gold quality
multicellular organism	UBERON:0000468	82.38	gold quality
substantia nigra	UBERON:0002038	82.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.21	gold quality
omental fat pad	UBERON:0010414	82.15	gold quality
rectum	UBERON:0001052	82.08	gold quality
stromal cell of endometrium	CL:0002255	82.07	gold quality
body of stomach	UBERON:0001161	82.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.02	gold quality
adrenal tissue	UBERON:0018303	82.02	gold quality
pancreas	UBERON:0001264	81.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.86	gold quality
minor salivary gland	UBERON:0001830	81.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.82	gold quality
lower esophagus	UBERON:0013473	81.79	gold quality
right lung	UBERON:0002167	81.68	gold quality
urinary bladder	UBERON:0001255	81.67	gold quality
mucosa of transverse colon	UBERON:0004991	81.60	gold quality
saliva-secreting gland	UBERON:0001044	81.57	gold quality
right coronary artery	UBERON:0001625	81.54	gold quality
fundus of stomach	UBERON:0001160	81.48	gold quality
apex of heart	UBERON:0002098	81.46	gold quality
islet of Langerhans	UBERON:0000006	81.43	gold quality
stomach	UBERON:0000945	81.41	gold quality
small intestine	UBERON:0002108	81.39	gold quality
left coronary artery	UBERON:0001626	81.32	gold quality
placenta	UBERON:0001987	81.16	gold quality
blood	UBERON:0000178	80.97	gold quality
tibial artery	UBERON:0007610	80.92	gold quality
popliteal artery	UBERON:0002250	80.91	gold quality
intestine	UBERON:0000160	80.89	gold quality
colon	UBERON:0001155	80.85	gold quality
esophagus	UBERON:0001043	80.84	gold quality
transverse colon	UBERON:0001157	80.84	gold quality
thoracic aorta	UBERON:0001515	80.73	gold quality
upper lobe of left lung	UBERON:0008952	80.72	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.67

HPA expression

RNA tissue specificity: Tissue enhanced

59 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Frontal cortex	tissue	22.4
Caudate putamen	tissue	21.3
Hippocampal formation	tissue	19.5
Cerebral cortex	tissue	17.2
Somatosensory cortex	tissue	17.2
Occipital cortex	tissue	17.0
Prefrontal cortex	tissue	16.8
Entorhinal cortex	tissue	16.2
Motor cortex	tissue	15.8
Retrosplenial and cingulate cortex	tissue	15.8
Hypothalamus	tissue	15.5
Thalamus	tissue	15.3
Temporal cortex	tissue	15.1
Retrosplenial cortex	tissue	15.0
Pons	tissue	14.6
Periaqueductal gray	tissue	14.6
Insular cortex	tissue	14.6
Amygdala	tissue	14.4
Olfactory bulb	tissue	14.4
Septum	tissue	14.3
Superior colliculi	tissue	13.9
Midbrain	tissue	13.8
Basal ganglia	tissue	13.7
Ventral forebrain	tissue	13.7
Substantia nigra	tissue	13.5
Cerebellum	tissue	13.3
Putamen	tissue	13.2
Medulla oblongata	tissue	13.1
Spinal cord	tissue	11.9
Corpus callosum	tissue	10.3
Pituitary gland	tissue	5.8
Vagina	tissue	3.7
Epididymis	tissue	1.1
Ovary	tissue	0.9
Pancreas	tissue	0.9
Thymus	tissue	0.7
Endometrium 1	tissue	0.6
Retina	tissue	0.5
Tonsil	tissue	0.5
Lymph node	tissue	0.3
Testis	tissue	0.3
Adipose tissue	tissue	0.3
Adrenal gland	tissue	0.3
Fallopian tube	tissue	0.3
Seminal vesicle	tissue	0.2
Lung	tissue	0.2
Stomach 1	tissue	0.1
Rectum	tissue	0.1
Parathyroid gland	tissue	0.1
Colon	tissue	0.1
Urinary bladder	tissue	0.1
Nucleus accumbens	tissue	0.1
Spleen	tissue	0.1
Liver	tissue	0.1
Kidney	tissue	0.1
Locus coeruleus	tissue	0.1
Hippocampus	tissue	0.1
Postcentral gyrus	tissue	0.1
Appendix	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 157; highest nTPM — Ventral hippocampus (19.5), Dorsal hippocampus (19.0), Subiculum (17.3), Dorsal spinal cord (11.9), Ventral spinal cord (11.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PRR3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 94 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-556-3P	99.74	68.75	1203

Functional genomics

gnomAD constraint: pLI 0.00249, LOEUF 0.965, missense Z 0.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000376560 — one region, missense o/e 0.92.

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prr3	ENSMUSG00000038500

Paralogs (2): ZC3H18 (ENSG00000158545), PPP1R10 (ENSG00000204569)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q7YR38	98.2%	Diamond
Macaca mulatta	Q5TM61	95.9%	Diamond
Rattus norvegicus	O55000	93.5%	Diamond
Sus scrofa	Q767L1	93.1%	Diamond
Xenopus laevis	Q6GLQ4	74.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ABCF1	protein-coding	23
GNL1	protein-coding	2794
MRPS18B	protein-coding	28973
PPP1R10	protein-coding	5514
HLA-E	protein-coding	3133
MIR877	ncRNA	100126314
ATAT1	protein-coding	79969
LINC02569	ncRNA	111082993

Protein

Protein identifiers

Proline-rich protein 3 — P79522 (reviewed: P79522)

Alternative names: MHC class I region proline-rich protein CAT56

All UniProt accessions (2): P79522, Q96QB9

Isoforms (2)

UniProt ID	Names	Canonical?
P79522-1	1	yes
P79522-2	2

RefSeq proteins (2): NP_001070965, NP_079539* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR042805	PRR3	Family

Pfam: PF00642

UniProt features (10 total): compositionally biased region 4, chain 1, zinc finger region 1, region of interest 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P79522-F1	61.18	0.06

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IF approved

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 (1)

Type	Positions
Pros-methylhistidine	180

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 190 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, ATF_B, TGGTGCT_MIR29A_MIR29B_MIR29C, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, CMYB_01, CREBP1_Q2, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, CREB_Q4, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, E4F1_Q6

GO Biological Process (1): positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled (GO:2000806)

GO Molecular Function (6): RNA binding (GO:0003723), protein phosphatase inhibitor activity (GO:0004864), zinc ion binding (GO:0008270), enzyme-substrate adaptor activity (GO:0140767), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), PTW/PP1 phosphatase complex (GO:0072357)

GO top-level categories

14 GO namespaces:

Category	Terms
termination of RNA polymerase II transcription, poly(A)-coupled	1
positive regulation of termination of RNA polymerase II transcription	1
regulation of termination of RNA polymerase II transcription, poly(A)-coupled	1
nucleic acid binding	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
transition metal ion binding	1
protein-macromolecule adaptor activity	1
binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
protein phosphatase type 1 complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 554 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRR3	MUCL3	Q3MIW9	550
PRR3	MRPS18B	Q9Y676	531
PRR3	PPP1R11	O60927	530
PRR3	GNL1	P36915	512
PRR3	TRIM10	Q9UDY6	503
PRR3	TRIM26	Q12899	466
PRR3	DHX16	O60231	455
PRR3	C5orf22	Q49AR2	390
PRR3	TRIM39	Q9HCM9	389
PRR3	CDSN	Q15517	362
PRR3	RPP21	Q9H633	332
PRR3	LILRA2	Q8N149	311
PRR3	SUPT7L	O94864	308
PRR3	PPP1R18	Q6NYC8	308
PRR3	OPRPN	P85047	292

IntAct

Human interaction partners of PRR3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

26 partners by confidence:

Partner	Interaction type	MIscore	Records
RBMY1F	physical association	0.780	7
HNRNPK	physical association	0.740	12
ASF1A	physical association	0.720	6
KHDRBS2	physical association	0.720	6
RBMX	physical association	0.720	6
KHDRBS3	physical association	0.670	3
RBMY1A1	physical association	0.560	6
TLE5	physical association	0.560	6
APOBEC3C	physical association	0.560	3
CCDC57	physical association	0.560	3
CLP1	physical association	0.560	3
FKBP1A	physical association	0.560	3
HSPA2	physical association	0.560	3
KLF1	physical association	0.560	3
KRTAP6-2	physical association	0.560	3
KRTAP6-3	physical association	0.560	3
MYPOP	physical association	0.560	3
NXF1	physical association	0.560	3
PSMA3	physical association	0.560	3
RAMAC	physical association	0.560	3
RBM3	physical association	0.560	3
SARS1	physical association	0.560	3
MRPS14	association	0.530	1
POLRMT	association	0.350	1
RBM47	association	0.350	1
ZNF316	association	0.350	1

BioGRID (273 interactions; top human partners by supporting records): HNRNPK (Two-hybrid; 4 records), NIFK (Affinity Capture-MS; 3 records), RBMX (Two-hybrid; 3 records), RPS2 (Affinity Capture-MS; 3 records), AES (Two-hybrid; 2 records), APOBEC3C (Two-hybrid; 2 records), ASF1A (Two-hybrid; 2 records), FGF8 (Affinity Capture-MS; 2 records), GLTSCR2 (Affinity Capture-MS; 2 records), HNRNPR (Affinity Capture-MS; 2 records), KHDRBS2 (Two-hybrid; 2 records), PTBP3 (Affinity Capture-MS; 2 records), RBMY1A1 (Two-hybrid; 2 records), RBMY1F (Two-hybrid; 2 records), ABCC2 (Co-fractionation)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	5	47.0×	7e-06
mRNA processing	5	15.1×	6e-04

Disease & clinical

Genetic variants

Variant evidence for PRR3: 39 ClinVar records (0 pathogenic / likely pathogenic); 19 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	5
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 301):

Position(s)	Effect	Δscore	Sites
6:30557414	donor_gain	1.0000
6:30557427	donor_gain	1.0000
6:30557439	donor_gain	1.0000
6:30557451–30557452	donor_loss	0.9900	6
6:30557468	donor_gain	0.9900
6:30562387–30562388	acceptor_loss	0.9900	6
6:30562386	acceptor_loss	0.9800
6:30557433	donor_gain	0.9600
6:30561567	donor_gain	0.9600
6:30561884	donor_gain	0.9600

AlphaMissense

236 missense substitutions predicted likely pathogenic (of 1,208 scored), across 56 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H180	8	0.975	0.995
F178	8	0.949	0.999
H163	8	0.946	0.991
C170	7	0.995	0.998
C176	7	0.995	0.998
C161	7	0.993	0.997
F164	7	0.987	0.997
W136	7	0.780	0.886
D154	7	0.776	0.901
G168	6	0.870	0.945
K155	6	0.865	0.947
P159	6	0.823	0.916
P181	6	0.813	0.908
N184	6	0.766	0.906
K167	6	0.753	0.873
D174	6	0.667	0.729
Y172	5	0.970	0.979
Y179	5	0.888	0.967
A177	5	0.846	0.970
S39	5	0.840	0.939

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

19 associations:

Study	Trait	p-value
GCST004521_15	Autism spectrum disorder or schizophrenia	1e-22
GCST004521_4	Autism spectrum disorder or schizophrenia	8e-20
GCST004521_70	Autism spectrum disorder or schizophrenia	6e-18
GCST004521_265	Autism spectrum disorder or schizophrenia	3e-17
GCST004521_38	Autism spectrum disorder or schizophrenia	7e-17
GCST004521_218	Autism spectrum disorder or schizophrenia	1e-16
GCST004521_153	Autism spectrum disorder or schizophrenia	2e-16
GCST004521_85	Autism spectrum disorder or schizophrenia	5e-16
GCST004521_154	Autism spectrum disorder or schizophrenia	2e-15
GCST004521_268	Autism spectrum disorder or schizophrenia	3e-15
GCST004521_86	Autism spectrum disorder or schizophrenia	5e-15
GCST004521_87	Autism spectrum disorder or schizophrenia	5e-15
GCST004521_122	Autism spectrum disorder or schizophrenia	4e-14
GCST004521_40	Autism spectrum disorder or schizophrenia	7e-14
GCST004521_272	Autism spectrum disorder or schizophrenia	3e-13
GCST004521_44	Autism spectrum disorder or schizophrenia	7e-11
GCST004521_183	Autism spectrum disorder or schizophrenia	2e-9
GCST005232_95	Neuroticism	8e-9
GCST004861_58	Itch intensity from mosquito bite	2e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0007660	neuroticism measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
dicrotophos	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
quercitrin	decreases expression	1
beta-lapachone	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
cylindrospermopsin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases response to substance	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Vincristine	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.