PAN2

Summary

PAN2 (poly(A) specific ribonuclease subunit PAN2, HGNC:20074) is a protein-coding gene on chromosome 12q13.3, encoding PAN2-PAN3 deadenylation complex catalytic subunit PAN2 (Q504Q3). Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover.

This gene encodes a deadenylase that functions as the catalytic subunit of the polyadenylate binding protein dependent poly(A) nuclease complex. The encoded protein is a magnesium dependent 3’ to 5’ exoribonuclease that is involved in the degradation of cytoplasmic mRNAs. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 9924 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple congenital anomalies/dysmorphic syndrome-intellectual disability (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 162 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 104
• MANE Select transcript: NM_014871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20074
Approved symbol	PAN2
Name	poly(A) specific ribonuclease subunit PAN2
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0710, hPAN2
Ensembl gene	ENSG00000135473
Ensembl biotype	protein_coding
OMIM	617447
Entrez	9924

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 29 protein_coding, 14 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000257931, ENST00000425394, ENST00000440411, ENST00000547100, ENST00000547226, ENST00000547518, ENST00000547572, ENST00000547994, ENST00000548043, ENST00000548982, ENST00000549073, ENST00000549090, ENST00000549348, ENST00000549964, ENST00000550028, ENST00000550555, ENST00000551359, ENST00000552630, ENST00000552868, ENST00000553230, ENST00000610546, ENST00000885816, ENST00000885817, ENST00000885818, ENST00000885819, ENST00000885820, ENST00000885821, ENST00000915376, ENST00000915377, ENST00000915378, ENST00000915379, ENST00000915380, ENST00000915381, ENST00000915382, ENST00000915383, ENST00000915384, ENST00000915385, ENST00000915386, ENST00000915387, ENST00000954123, ENST00000954124, ENST00000954125, ENST00000954126, ENST00000954127

RefSeq mRNA: 13 — MANE Select: NM_014871 NM_001127460, NM_001166279, NM_001394699, NM_001394700, NM_001394701, NM_001394702, NM_001394703, NM_001394704, NM_001394705, NM_001394706, NM_001394707, NM_001394708, NM_014871

CCDS: CCDS44922, CCDS53802, CCDS8915

Canonical transcript exons

ENST00000440411 — 26 exons

Exon	Start	End
ENSE00001182399	56324049	56324185
ENSE00003461465	56327364	56327631
ENSE00003462581	56328238	56328358
ENSE00003464269	56322615	56322758
ENSE00003476400	56324294	56324493
ENSE00003480664	56323311	56323384
ENSE00003490708	56319308	56319487
ENSE00003494556	56319088	56319181
ENSE00003541356	56327995	56328072
ENSE00003547238	56322078	56322168
ENSE00003549678	56322423	56322482
ENSE00003561010	56325009	56325128
ENSE00003561715	56328472	56328641
ENSE00003568151	56324581	56324709
ENSE00003569375	56326617	56326959
ENSE00003587521	56319621	56319764
ENSE00003587644	56332813	56333208
ENSE00003594485	56323062	56323209
ENSE00003605855	56325335	56325454
ENSE00003612156	56323500	56323598
ENSE00003619315	56318237	56318434
ENSE00003640310	56326313	56326409
ENSE00003666483	56323807	56323913
ENSE00003669084	56319864	56320021
ENSE00003679814	56316936	56317643
ENSE00003931853	56333862	56334000

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0622 / max 116.3661, expressed in 1676 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131515	8.9032	1672
131514	0.1591	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	98.90	gold quality
left lobe of thyroid gland	UBERON:0001120	98.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.70	gold quality
right uterine tube	UBERON:0001302	98.58	gold quality
cerebellar hemisphere	UBERON:0002245	98.39	gold quality
cerebellar cortex	UBERON:0002129	98.29	gold quality
left ovary	UBERON:0002119	98.25	gold quality
adenohypophysis	UBERON:0002196	98.21	gold quality
right ovary	UBERON:0002118	98.05	gold quality
body of pancreas	UBERON:0001150	98.01	gold quality
thyroid gland	UBERON:0002046	97.91	gold quality
metanephros cortex	UBERON:0010533	97.90	gold quality
right testis	UBERON:0004534	97.89	gold quality
left testis	UBERON:0004533	97.87	gold quality
right lobe of liver	UBERON:0001114	97.75	gold quality
tibial nerve	UBERON:0001323	97.66	gold quality
pituitary gland	UBERON:0000007	97.56	gold quality
body of uterus	UBERON:0009853	97.42	gold quality
endocervix	UBERON:0000458	97.22	gold quality
mucosa of stomach	UBERON:0001199	97.20	gold quality
right adrenal gland	UBERON:0001233	97.05	gold quality
right adrenal gland cortex	UBERON:0035827	96.93	gold quality
apex of heart	UBERON:0002098	96.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.79	gold quality
cerebellum	UBERON:0002037	96.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.74	gold quality
body of stomach	UBERON:0001161	96.71	gold quality
lower esophagus	UBERON:0013473	96.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.53	gold quality
ectocervix	UBERON:0012249	96.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.07
E-MTAB-7303	no	278.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting PAN2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-125A-5P	99.36	70.59	1640

Literature-anchored findings (GeneRIF, showing 6)

• hPan2 and hPan3 have roles in mRNA decay and exhibit cytoplasmic co-localization (PMID:14583602)
• USP52 is a key component of P-bodies required to prevent HIF1A mRNA degradation (PMID:23398456)
• USP52 is a bona fide ubiquitin-specific protease, and USP52 promotes ASF1A deubiquitination and stabilization. (PMID:29599486)
• USP52 regulates DNA end resection and chemosensitivity through removing inhibitory ubiquitination from CtIP. (PMID:33097710)
• USP52 inhibits cell proliferation by stabilizing PTEN protein in non-small cell lung cancer. (PMID:34533198)
• Biallelic PAN2 variants in individuals with a syndromic neurodevelopmental disorder and multiple congenital anomalies. (PMID:35304602)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pan2	ENSDARG00000074675
mus_musculus	Pan2	ENSMUSG00000005682
rattus_norvegicus	Pan2	ENSRNOG00000032441
drosophila_melanogaster	PAN2	FBGN0033352
caenorhabditis_elegans		WBGENE00017951

Protein

Protein identifiers

PAN2-PAN3 deadenylation complex catalytic subunit PAN2 — Q504Q3 (reviewed: Q504Q3)

Alternative names: Inactive ubiquitin carboxyl-terminal hydrolase 52, PAB1P-dependent poly(A)-specific ribonuclease, Poly(A)-nuclease deadenylation complex subunit 2

All UniProt accessions (2): Q504Q3, F8VXK8

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3’-5’ exonucleolytic degradation, or deadenylation-dependent mRNA decaping and subsequent 5’-3’ exonucleolytic degradation by XRN1. Also acts as an important regulator of the HIF1A-mediated hypoxic response. Required for HIF1A mRNA stability independent of poly(A) tail length regulation.

Subunit / interactions. Forms a heterotrimer with an asymmetric homodimer of the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex. Interacts with PAN3 isoform 1/Pan3L and isoform 3/Pan3S. Interacts with ZFP36.

Subcellular location. Cytoplasm. P-body. Nucleus.

Activity regulation. Positively regulated by the regulatory subunit PAN3.

Cofactor. Binds 2 metal cations per subunit in the catalytic exonuclease domain.

Domain organisation. Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex. The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3.

Similarity. Belongs to the peptidase C19 family. PAN2 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q504Q3-1	1	yes
Q504Q3-2	2
Q504Q3-3	3

RefSeq proteins (13): NP_001120932, NP_001159751, NP_001381628, NP_001381629, NP_001381630, NP_001381631, NP_001381632, NP_001381633, NP_001381634, NP_001381635, NP_001381636, NP_001381637, NP_055686* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR013520	Ribonucl_H	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR028881	PAN2_UCH_dom	Domain
IPR028889	USP	Domain
IPR030843	PAN2	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR048841	PAN2_N	Domain
IPR050785	PAN2-PAN3_catalytic_subunit	Family

Pfam: PF00929, PF13423, PF20770

Enzyme classification (BRENDA):

• EC 3.1.13.4 — poly(A)-specific ribonuclease (BRENDA: 15 organisms, 67 substrates, 89 inhibitors, 9 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
POLY(A) RNA	—	7
POLY(A)	0.0051	1

UniProt features (22 total): repeat 4, binding site 4, sequence variant 3, modified residue 2, splice variant 2, sequence conflict 2, domain 2, chain 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9QTU	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q504Q3-F1	79.58	0.37

Functional residue map

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

Ligand- & substrate-binding residues (4): 1087; 1139; 978; 980

Post-translational modifications (2): 791, 1189

Mutagenesis-validated functional residues (1):

Position	Phenotype
1087	loss of exonuclease activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-429947	Deadenylation of mRNA

MSigDB gene sets: 276 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, E2F_Q4, CREL_01, E2F_Q4_01, GOMF_RNA_NUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_P_BODY_ASSEMBLY, E2F4DP1_01, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (4): nuclear-transcribed mRNA poly(A) tail shortening (GO:0000289), mRNA processing (GO:0006397), positive regulation of cytoplasmic mRNA processing body assembly (GO:0010606), nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288)

GO Molecular Function (8): 3’-5’-RNA exonuclease activity (GO:0000175), nucleic acid binding (GO:0003676), poly(A)-specific ribonuclease activity (GO:0004535), metal ion binding (GO:0046872), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): P-body (GO:0000932), nucleus (GO:0005634), cytosol (GO:0005829), PAN complex (GO:0031251), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deadenylation-dependent mRNA decay	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear-transcribed mRNA catabolic process	2
binding	2
cytoplasm	2
cellular anatomical structure	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
RNA processing	1
mRNA metabolic process	1
regulation of cytoplasmic mRNA processing body assembly	1
P-body assembly	1
positive regulation of organelle assembly	1
mRNA destabilization	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
3’-5’-RNA exonuclease activity	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
exoribonuclease complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1463 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAN2	USP50	Q70EL3	718
PAN2	USP54	Q70EL1	660
PAN2	USP43	Q70EL4	610
PAN2	USP39	Q53GS9	604
PAN2	USPL1	Q5W0Q7	568
PAN2	PABPC4L	P0CB38	565
PAN2	PABPC1L	Q4VXU2	554
PAN2	USP53	Q70EK8	552
PAN2	PABPC3	Q9H361	548
PAN2	USP38	Q8NB14	545
PAN2	PABPC1L2A	Q5JQF8	537
PAN2	PABPC4	Q13310	535
PAN2	PABPC5	Q96DU9	531
PAN2	PABPC1	P11940	531
PAN2	ZUP1	Q96AP4	518

IntAct

57 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
PAN3	PAN2	psi-mi:“MI:0915”(physical association)	0.740
PAN2	PAN3	psi-mi:“MI:0915”(physical association)	0.740
PAN3	PAN2	psi-mi:“MI:0403”(colocalization)	0.740
TNRC6C	CNOT1	psi-mi:“MI:0914”(association)	0.690
ASF1B	HAT1	psi-mi:“MI:0914”(association)	0.640
ASF1A	HAT1	psi-mi:“MI:0914”(association)	0.640
TNRC6C	CNOT1	psi-mi:“MI:0914”(association)	0.620
ASF1A	MCM4	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
TNRC6C	PAN2	psi-mi:“MI:0914”(association)	0.530
TNRC6C	PAN2	psi-mi:“MI:0915”(physical association)	0.500
TNRC6C	CNOT3	psi-mi:“MI:0914”(association)	0.460
PAN2	ARCN1	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
DDX6	EIF3CL	psi-mi:“MI:0914”(association)	0.350
GSPT1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
PABPC4	HNRNPR	psi-mi:“MI:0914”(association)	0.350
CADPS	ACOT7	psi-mi:“MI:0914”(association)	0.350
CLIC3	CNOT4	psi-mi:“MI:0914”(association)	0.350
PAN2		psi-mi:“MI:0914”(association)	0.350
PAN3		psi-mi:“MI:0914”(association)	0.350

BioGRID (422): PAN2 (Reconstituted Complex), PAN2 (Affinity Capture-Western), PAN2 (Affinity Capture-Western), PAN2 (Affinity Capture-Western), PAN2 (Affinity Capture-Western), ZFP36 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), PAN2 (Affinity Capture-MS), PAN2 (Affinity Capture-MS), KIAA0430 (Affinity Capture-MS), PAN2 (Affinity Capture-MS), NISCH (Affinity Capture-MS), PAN2 (Affinity Capture-MS), PAN2 (Affinity Capture-MS), PCGF5 (Affinity Capture-MS)

ESM2 similar proteins: A0A8J1LLF7, A0A974H8H3, A0MQH0, A4FUD6, A5HK05, B3DLA6, P11029, P11497, P42694, P54198, Q13085, Q25BN1, Q28559, Q4R4U1, Q504Q3, Q5R5F8, Q5R660, Q5R8I6, Q5RCC1, Q5SWU9, Q5ZIT8, Q6DFV5, Q6IE70, Q6NYU2, Q6P1X5, Q6TUI4, Q6TV19, Q80YV4, Q8BGF7, Q8BHL5, Q8BPU7, Q8C176, Q8CIQ7, Q8IZD9, Q8K0F1, Q8R418, Q8R5L3, Q8VHE0, Q923S8, Q92556

Diamond homologs: A1A5R7, A1Z7K9, A3KPE8, A3LRV8, A4RF51, A5DAD0, A5E1W0, B2GUW6, G0SAK8, O94375, O94443, P0C581, P0CQ08, P0CQ09, P0CQ44, P0CQ45, P48778, P53010, P53015, P53331, Q08237, Q09798, Q0CJU7, Q10124, Q2GSV2, Q2T9U5, Q2YDK1, Q3U1G5, Q4PER6, Q4R9F7, Q4WYA1, Q504Q3, Q54U94, Q5AL29, Q5APK0, Q5B367, Q5F450, Q5REE2, Q6AXU3, Q6C462

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ATM	“up-regulates activity”	PAN2	phosphorylation
PAN2	“up-regulates activity”	RBBP8	deubiquitination
PAN2	“form complex”	“PAN2-PAN3 deadenylation complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	132
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4526897	NM_014871.6(PAN2):c.3153del (p.Ser1052fs)	Pathogenic
4526900	NM_014871.6(PAN2):c.3026T>A (p.Val1009Asp)	Pathogenic
4688405	NM_014871.6(PAN2):c.3354G>A (p.Trp1118Ter)	Pathogenic
1342925	NM_014871.6(PAN2):c.574-2A>G	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

7909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56318274:C:A	W1179C	1.000
12:56318274:C:G	W1179C	1.000
12:56318276:A:G	W1179R	1.000
12:56318276:A:T	W1179R	1.000
12:56318290:C:T	G1174D	1.000
12:56318291:C:G	G1174R	1.000
12:56318374:A:G	L1146P	1.000
12:56318374:A:T	L1146Q	1.000
12:56318380:A:G	L1144P	1.000
12:56318383:G:T	A1143D	1.000
12:56318392:G:T	A1140D	1.000
12:56318393:C:G	A1140P	1.000
12:56318394:A:C	D1139E	1.000
12:56318394:A:T	D1139E	1.000
12:56318395:T:A	D1139V	1.000
12:56318395:T:C	D1139G	1.000
12:56318395:T:G	D1139A	1.000
12:56318396:C:G	D1139H	1.000
12:56318403:A:C	S1136R	1.000
12:56318403:A:T	S1136R	1.000
12:56318405:T:G	S1136R	1.000
12:56318409:A:C	H1134Q	1.000
12:56318409:A:T	H1134Q	1.000
12:56318411:G:C	H1134D	1.000
12:56318421:T:A	Q1130H	1.000
12:56318421:T:G	Q1130H	1.000
12:56319102:G:T	A1121D	1.000
12:56319103:C:G	A1121P	1.000
12:56319105:A:G	L1120P	1.000
12:56319105:A:T	L1120H	1.000

dbSNP variants (sampled 300 via entrez): RS1000057247 (12:56331583 C>T), RS1000193082 (12:56326423 T>C,G), RS1000288229 (12:56326787 G>A), RS1000354501 (12:56318530 T>A), RS1000459548 (12:56325300 C>T), RS1000513415 (12:56331817 G>A), RS1000656721 (12:56333348 A>G,T), RS1000664012 (12:56317908 G>A), RS1000680863 (12:56317021 G>A), RS1001056227 (12:56316740 G>A,T), RS1001426770 (12:56330765 T>C), RS1001466331 (12:56333232 A>C,G), RS1001494557 (12:56316635 C>T), RS1001889780 (12:56334217 A>G), RS1002012182 (12:56324819 G>A)

Disease associations

OMIM: gene MIM:617447 | disease phenotypes: MIM:621384

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple congenital anomalies/dysmorphic syndrome-intellectual disability	Definitive	Autosomal recessive
syndromic disease	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Moderate	AR

Mondo (3): developmental delay with variable cardiac and renal congenital anomalies and dysmorphic facies (MONDO:0980727), syndromic disease (MONDO:0002254), multiple congenital anomalies/dysmorphic syndrome-intellectual disability (MONDO:0015159)

Orphanet (0):

HPO phenotypes

104 total (30 of 104 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000081	Duplicated collecting system
HP:0000083	Renal insufficiency
HP:0000086	Ectopic kidney
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000243	Trigonocephaly
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000274	Small face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000463	Anteverted nares

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002115_16	Axial length	4.000000e-07
GCST002702_12	Height	7.000000e-35
GCST010002_217	Refractive error	6.000000e-174
GCST011972_9	Height	4.000000e-57
GCST90090967_24	Height	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	5
methacrylaldehyde	affects cotreatment, increases expression, decreases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, decreases expression, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Ozone	increases abundance, affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	increases expression, increases phosphorylation	2
Aflatoxin B1	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C3KZ	N/Tert-1 USP52	Telomerase immortalized cell line	Male
CVCL_TC01	HAP1 PAN2 (-) 1	Cancer cell line	Male
CVCL_TC02	HAP1 PAN2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome