PRIM2

Summary

PRIM2 (DNA primase subunit 2, HGNC:9370) is a protein-coding gene on chromosome 6p11.2, encoding DNA primase large subunit (P49643). Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes the 58 kilodalton subunit of DNA primase, an enzyme that plays a key role in the replication of DNA. The encoded protein forms a heterodimer with a 49 kilodalton subunit. This heterodimer functions as a DNA-directed RNA polymerase to synthesize small RNA primers that are used to create Okazaki fragments on the lagging strand of the DNA. Alternative splicing of this gene results in multiple transcript variants. This gene has a related pseudogene, which is also present on chromosome 6.

Source: NCBI Gene 5558 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_000947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9370
Approved symbol	PRIM2
Name	DNA primase subunit 2
Location	6p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000146143
Ensembl biotype	protein_coding
OMIM	176636
Entrez	5558

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000274891, ENST00000370687, ENST00000419977, ENST00000470638, ENST00000490313, ENST00000550475, ENST00000615550, ENST00000671770, ENST00000672107, ENST00000934977, ENST00000934978, ENST00000934979, ENST00000934980

RefSeq mRNA: 3 — MANE Select: NM_000947 NM_000947, NM_001282487, NM_001282488

CCDS: CCDS75476, CCDS75477

Canonical transcript exons

ENST00000615550 — 14 exons

Exon	Start	End
ENSE00002425964	57537440	57537625
ENSE00003713374	57606375	57606457
ENSE00003719061	57532411	57532483
ENSE00003719133	57382031	57382168
ENSE00003722747	57645928	57646850
ENSE00003727335	57507387	57507454
ENSE00003734777	57379901	57379996
ENSE00003735385	57632133	57632201
ENSE00003735855	57320457	57320560
ENSE00003738215	57324201	57324280
ENSE00003745149	57325925	57326045
ENSE00003749833	57601093	57601219
ENSE00003751924	57318437	57318599
ENSE00003844426	57317630	57317701

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 92.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6502 / max 842.0722, expressed in 1795 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68338	25.1289	1795
68339	0.5213	252

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.93	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.15	gold quality
ganglionic eminence	UBERON:0004023	86.54	gold quality
calcaneal tendon	UBERON:0003701	86.01	gold quality
ventricular zone	UBERON:0003053	85.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.93	gold quality
oocyte	CL:0000023	84.75	gold quality
colonic epithelium	UBERON:0000397	82.84	gold quality
stromal cell of endometrium	CL:0002255	81.81	gold quality
cortical plate	UBERON:0005343	80.54	gold quality
rectum	UBERON:0001052	79.97	gold quality
adrenal tissue	UBERON:0018303	79.61	gold quality
sural nerve	UBERON:0015488	78.16	gold quality
mucosa of transverse colon	UBERON:0004991	77.67	gold quality
islet of Langerhans	UBERON:0000006	77.62	gold quality
bone marrow cell	CL:0002092	77.49	gold quality
leukocyte	CL:0000738	77.39	gold quality
monocyte	CL:0000576	77.14	gold quality
mononuclear cell	CL:0000842	77.05	gold quality
lymph node	UBERON:0000029	76.82	gold quality
body of uterus	UBERON:0009853	76.62	gold quality
granulocyte	CL:0000094	76.47	gold quality
smooth muscle tissue	UBERON:0001135	76.37	gold quality
tibial artery	UBERON:0007610	76.21	gold quality
popliteal artery	UBERON:0002250	76.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.66	gold quality
ectocervix	UBERON:0012249	75.60	gold quality
transverse colon	UBERON:0001157	75.47	gold quality
aorta	UBERON:0000947	75.44	gold quality
prostate gland	UBERON:0002367	75.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4

miRNA regulators (miRDB)

58 targeting PRIM2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-330-3P	99.41	69.95	2521

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• analysis of the iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase (PMID:17893144)
• p58C(C-terminal regulatory domain of the large subunit) structure reveals a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure. (PMID:20643958)
• The fragment that forms a beta-sheet in the reported structure p58C/3L9Q of the same human primase domain is folded in three alpha-helices in our p58C/3Q36 structure, similarly to yeast primase. (PMID:21346410)
• PRIM2 gene is not imprinted in the placenta. (PMID:22437878)
• the N-terminal domain of the large subunit of primase (p58N) directly interacts with the C-terminal domain of the catalytic subunit of polalpha (p180C) (PMID:24962573)
• Data indicate that the conformational changes in primase are necessary to accomplish the initiation and then elongation of RNA synthesis. (PMID:25550159)
• Data suggest that PRIM1-p58,C-terminal domain stays bound to initiating NTP and 3prime-overhang DNA during whole cycle of RNA primer synthesis; meanwhile, PRIM1-p49 slides along DNA template toward 5prime-end with PRIM1-p58,N-terminal domain attached. (PMID:26710848)
• Study results show that although human DNA primase C-terminal domain (p58C) can be stabilized in different conformations in the crystalline state, in solution there is effectively no difference in the structure and functional properties of p58C constructs of different lengths. (PMID:30562384)
• Genetic variants of CHEK1, PRIM2 and CDK6 in the mitotic phase-related pathway are associated with nonsmall cell lung cancer survival. (PMID:34058013)
• PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients. (PMID:38423596)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prim2	ENSDARG00000052721
mus_musculus	Prim2	ENSMUSG00000026134
rattus_norvegicus	Prim2	ENSRNOG00000012486
drosophila_melanogaster	Prim2	FBGN0259676
caenorhabditis_elegans	pri-2	WBGENE00004181

Protein

Protein identifiers

DNA primase large subunit — P49643 (reviewed: P49643)

Alternative names: DNA primase 58 kDa subunit

All UniProt accessions (4): P49643, A0A096LP51, A0A5F9ZHR0, A0A5F9ZHU7

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit. Binds RNA:DNA duplex and coordinates the catalytic activities of PRIM1 and POLA2 during primase-to-polymerase switch.

Subunit / interactions. Heterodimer of a catalytic subunit PRIM1 and a regulatory subunit PRIM2, also known as the DNA primase complex. Interacts via (C-terminus) with PRIM1. Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively. Within the complex, POLA1 directly interacts with PRIM2.

Cofactor. Binds 1 [4Fe-4S] cluster.

Domain organisation. The RNA:DNA duplex-binding domain interacts with the template phosphates at positions -2, -1, 1, and 2 positioning its bases -1, 1, and 2 for duplex formation. Interacts only with the beta- and gamma-phosphates of triphosphate moiety of initiating NTP of the primer. The side chain of His-303 mimics a RNA base that would be paired with the template nucleotide at position -1 via a hydrogen bond, thereby facilitating the stacking of the initiating NTP. In the initiating primosome a ‘mini RNA:DNA’ duplex is formed comprising three template nucleotides at positions -1, 1, and 2 on one strand and His-303, initiating NTP, and incoming NTP on the other strand. The interdomain linker provides flexibility in movement relative to primosome platform composed of PRIM1, the N-terminus of PRIM2, the C-terminus of POLA1 and POLA2. Together with POLA1 interdomain linker, allows for large-scale conformational changes of primosome and coordinated autoregulation of catalytic centers of PRIM1 and POLA1. It is proposed to move the C-terminus of PRIM2 close to PRIM1 during initiation, then move it away with the 5’-end of the nascent primer during elongation. The steric hindrance between the N- and C-terminus of PRIM2 as the RNA primer is elongated limits its length to 9 nucleotides. Ultimately a large rotation of the C-terminus of PRIM2 transfers the primer to POLA1 active site for DNA synthesis.

Similarity. Belongs to the eukaryotic-type primase large subunit family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49643-1	1	yes
P49643-2	2

RefSeq proteins (3): NP_000938, NP_001269416, NP_001269417 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007238	DNA_primase_lsu_euk/arc	Family
IPR016558	DNA_primase_lsu_euk	Family
IPR058560	DNA_primase_C	Domain

Pfam: PF04104, PF26466

Enzyme classification (BRENDA):

• EC 2.7.7.102 — DNA primase AEP (BRENDA: 9 organisms, 25 substrates, 3 inhibitors, 8 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DNTP	5–198	3
5’-CTTCTTCTGTGC-3’	0.2	1
ATP	0.15	1
DATP	0.032	1
NTP	27.5	1

UniProt features (66 total): helix 23, strand 12, sequence variant 7, mutagenesis site 5, region of interest 4, turn 4, binding site 4, sequence conflict 3, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
3L9Q	X-RAY DIFFRACTION	1.7
5I7M	X-RAY DIFFRACTION	1.93
6DHW	X-RAY DIFFRACTION	2.01
5F0Q	X-RAY DIFFRACTION	2.21
5DQO	X-RAY DIFFRACTION	2.3
3Q36	X-RAY DIFFRACTION	2.5
4RR2	X-RAY DIFFRACTION	2.65
4BPU	X-RAY DIFFRACTION	2.7
8VY3	ELECTRON MICROSCOPY	2.98
5F0S	X-RAY DIFFRACTION	3
4BPW	X-RAY DIFFRACTION	3
8QJ7	ELECTRON MICROSCOPY	3.07
8D96	ELECTRON MICROSCOPY	3.35
9C8V	ELECTRON MICROSCOPY	3.39
4BPX	X-RAY DIFFRACTION	3.4
8B9D	ELECTRON MICROSCOPY	3.4
8D0B	ELECTRON MICROSCOPY	3.43
8D9D	ELECTRON MICROSCOPY	3.59
5EXR	X-RAY DIFFRACTION	3.6
7OPL	ELECTRON MICROSCOPY	4.12
8D0K	ELECTRON MICROSCOPY	4.27
7U5C	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49643-F1	81.11	0.49

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): 287; 367; 384; 424

Post-translational modifications (1): 470

Mutagenesis-validated functional residues (5):

Position	Phenotype
97	decreases primase affinity for pola1 by 10-fold.
104	decreases primase affinity for pola1 by 40-fold.
107	decreases primase affinity for pola1 by 30-fold.
108	decreases primase affinity for pola1 by 40-fold.
256–270	decreases rna primer di-nucleotide formation about 5-fold. does not affect the ratio between the di-nucleotide and its e

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-113501	Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-174411	Polymerase switching on the C-strand of the telomere
R-HSA-174430	Telomere C-strand synthesis initiation
R-HSA-68952	DNA replication initiation
R-HSA-68962	Activation of the pre-replicative complex
R-HSA-69091	Polymerase switching
R-HSA-69166	Removal of the Flap Intermediate
R-HSA-69183	Processive synthesis on the lagging strand
R-HSA-9710421	Defective pyroptosis

MSigDB gene sets: 291 (showing top): REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, REACTOME_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, MORF_MSH3, PAL_PRMT5_TARGETS_UP, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MORF_RAD51L3, GOLDRATH_ANTIGEN_RESPONSE, PATIL_LIVER_CANCER, WEI_MYCN_TARGETS_WITH_E_BOX, GOCC_NUCLEAR_REPLICATION_FORK, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN

GO Biological Process (3): DNA replication, synthesis of primer (GO:0006269), DNA replication initiation (GO:0006270), DNA replication (GO:0006260)

GO Molecular Function (7): DNA binding (GO:0003677), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), DNA/RNA hybrid binding (GO:0071667), DNA-directed RNA polymerase activity (GO:0003899), protein binding (GO:0005515), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (2): nucleoplasm (GO:0005654), alpha DNA polymerase:primase complex (GO:0005658)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Telomere C-strand (Lagging Strand) Synthesis	2
Lagging Strand Synthesis	2
E2F mediated regulation of DNA replication	1
Synthesis of DNA	1
DNA Replication Pre-Initiation	1
G1/S Transition	1
Leading Strand Synthesis	1
Processive synthesis on the lagging strand	1
Diseases of programmed cell death	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated DNA replication	2
RNA biosynthetic process	2
DNA metabolic process	2
nucleic acid binding	2
DNA biosynthetic process	1
cation binding	1
iron-sulfur cluster binding	1
5’-3’ RNA polymerase activity	1
binding	1
metal cluster binding	1
nuclear lumen	1
cellular anatomical structure	1
DNA polymerase complex	1
nuclear replisome	1
nuclear DNA-directed RNA polymerase complex	1

Protein interactions and networks

STRING

2134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRIM2	PRIM1	P49642	999
PRIM2	POLA2	Q14181	998
PRIM2	POLA1	P09884	991
PRIM2	POLD1	P28340	747
PRIM2	POLE2	P56282	649
PRIM2	POLE3	Q9NRF9	632
PRIM2	RNASEH2A	O75792	610
PRIM2	MCM4	P33991	593
PRIM2	RFC3	P40938	572
PRIM2	CDC45	O75419	561
PRIM2	POLD2	P49005	561
PRIM2	DNA2	P51530	559
PRIM2	CCNB1	P14635	551
PRIM2	WDHD1	O75717	532
PRIM2	MCM10	Q7L590	532

IntAct

93 interactions, top by confidence:

A	B	Type	Score
MMS19	CIAO1	psi-mi:“MI:0914”(association)	0.910
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
BTF3L4	TXLNA	psi-mi:“MI:0914”(association)	0.780
PRIM1	PRIM2	psi-mi:“MI:0915”(physical association)	0.740
MMS19	ERCC2	psi-mi:“MI:0914”(association)	0.690
PRPS2	PRPSAP2	psi-mi:“MI:0914”(association)	0.670
rep	POLA1	psi-mi:“MI:0914”(association)	0.670
PRIM1	POLA1	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
POLA1	PRIM1	psi-mi:“MI:0914”(association)	0.640
PRIM2	RECK	psi-mi:“MI:0915”(physical association)	0.560
PRIM2	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ERP44	MEX3A	psi-mi:“MI:0914”(association)	0.530
RNF31	GBP1	psi-mi:“MI:0914”(association)	0.530
rep	POLA1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
PM20D2	PRIM2	psi-mi:“MI:0914”(association)	0.530
BTF3L4	PRIM1	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530

BioGRID (154): PRIM2 (Affinity Capture-RNA), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-Western), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Proximity Label-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS)

ESM2 similar proteins: A7TTC4, A8XAA9, O02328, O02334, O14215, O74516, O74761, O74927, O81395, O89044, P09810, P09880, P10363, P17290, P17532, P20457, P20664, P33610, P33755, P34466, P34529, P38025, P40383, P49643, P51820, Q0W2J3, Q10313, Q24317, Q2KIH7, Q2QRX6, Q55BM5, Q5F408, Q6DJ95, Q6FWT4, Q6PA41, Q756A7, Q7ZWR2, Q84WJ2, Q8NIZ4, Q8RWT8

Diamond homologs: O02334, O74761, O89044, P20457, P33610, P49643, Q55BM5, Q84WJ2, Q9VPH2, Q8NIZ4, Q97BA1, Q0W2J3, Q12U19, Q8TVJ5, Q9HJD1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
clofarabine	“down-regulates activity”	PRIM2	“chemical inhibition”
PRIM2	“form complex”	“DNA primase complex”	binding
“iron-sulfur cluster”	“up-regulates activity”	PRIM2	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2039 predictions. Top by Δscore:

Variant	Effect	Δscore
6:57320452:TTTA:T	acceptor_loss	1.0000
6:57320453:TTA:T	acceptor_loss	1.0000
6:57320455:A:AG	acceptor_gain	1.0000
6:57320455:A:T	acceptor_loss	1.0000
6:57320455:AGT:A	acceptor_gain	1.0000
6:57320456:G:A	acceptor_loss	1.0000
6:57320456:G:GG	acceptor_gain	1.0000
6:57320456:GT:G	acceptor_gain	1.0000
6:57320456:GTG:G	acceptor_gain	1.0000
6:57320456:GTGT:G	acceptor_gain	1.0000
6:57320456:GTGTT:G	acceptor_gain	1.0000
6:57320556:ACAGA:A	donor_gain	1.0000
6:57320557:CAGA:C	donor_gain	1.0000
6:57320558:AGA:A	donor_gain	1.0000
6:57320559:GA:G	donor_gain	1.0000
6:57320559:GAG:G	donor_gain	1.0000
6:57320560:AG:A	donor_loss	1.0000
6:57320561:G:GG	donor_gain	1.0000
6:57320561:GT:G	donor_loss	1.0000
6:57324183:T:G	acceptor_gain	1.0000
6:57324199:A:G	acceptor_gain	1.0000
6:57324200:G:GG	acceptor_gain	1.0000
6:57324200:G:GT	acceptor_loss	1.0000
6:57324276:CAGTC:C	donor_gain	1.0000
6:57324278:GTC:G	donor_gain	1.0000
6:57324281:G:GG	donor_gain	1.0000
6:57325918:A:AG	acceptor_gain	1.0000
6:57325920:TTCA:T	acceptor_loss	1.0000
6:57325921:TCAGT:T	acceptor_loss	1.0000
6:57325922:CA:C	acceptor_loss	1.0000

AlphaMissense

3381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:57325966:T:C	L127P	1.000
6:57537464:T:C	C287R	1.000
6:57537503:C:G	H300D	1.000
6:57537522:G:C	R306P	1.000
6:57537547:G:C	K314N	1.000
6:57537547:G:T	K314N	1.000
6:57537572:G:C	A323P	1.000
6:57537584:T:A	W327R	1.000
6:57537584:T:C	W327R	1.000
6:57601120:C:A	R350S	1.000
6:57601121:G:C	R350P	1.000
6:57601123:C:G	H351D	1.000
6:57601133:G:A	G354E	1.000
6:57601133:G:T	G354V	1.000
6:57601142:G:A	G357D	1.000
6:57601171:T:C	C367R	1.000
6:57606377:T:C	C384R	1.000
6:57632170:C:A	A423D	1.000
6:57318582:C:A	A46D	0.999
6:57318591:G:C	R49T	0.999
6:57318591:G:T	R49I	0.999
6:57318592:A:C	R49S	0.999
6:57318592:A:T	R49S	0.999
6:57320460:T:C	L53S	0.999
6:57320469:T:A	V56D	0.999
6:57324246:T:C	S102P	0.999
6:57324249:C:G	H103D	0.999
6:57324252:T:C	F104L	0.999
6:57324254:T:A	F104L	0.999
6:57324254:T:G	F104L	0.999

dbSNP variants (sampled 300 via entrez): RS1000004170 (6:57383656 G>T), RS1000006515 (6:57221885 C>G), RS1000010060 (6:57334781 A>T), RS1000031441 (6:57291632 A>T), RS1000078177 (6:57335897 G>A), RS1000093833 (6:57221724 A>C,G), RS1000109874 (6:57339525 A>G), RS1000117104 (6:57266252 G>A), RS1000139224 (6:57269549 G>C), RS1000146286 (6:57456696 T>A,G), RS1000178355 (6:57240229 G>A), RS1000191351 (6:57351692 A>G), RS1000197449 (6:57420519 A>G), RS1000218098 (6:57317561 C>A), RS1000219406 (6:57435821 T>C)

Disease associations

OMIM: gene MIM:176636 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002444_3	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	4.000000e-06
GCST005752_153	Systemic lupus erythematosus	6.000000e-07
GCST007576_278	Chronotype	8.000000e-13
GCST010866_114	Coronary artery disease	2.000000e-17
GCST011365_98	Myocardial infarction	7.000000e-08
GCST011494_31	Daytime nap	8.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0008328	chronotype measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2363042 (PROTEIN FAMILY)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	4
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation, increases expression	3
manganese chloride	increases expression, decreases expression, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Manganese	increases abundance, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
VX-agent	increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, decreases expression	1
NSC668394	increases expression	1
Dasatinib	decreases expression	1

Clinical trials (associated diseases)

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