WRNIP1

Summary

WRNIP1 (WRN helicase interacting protein 1, HGNC:20876) is a protein-coding gene on chromosome 6p25.2, encoding ATPase WRNIP1 (Q96S55). Functions as a modulator of initiation or reinitiation events during DNA polymerase delta-mediated DNA synthesis.

Werner’s syndrome is a rare autosomal recessive disorder characterized by accelerated aging that is caused by defects in the Werner syndrome ATP-dependent helicase gene (WRN). The protein encoded by this gene interacts with the exonuclease-containing N-terminal portion of the Werner protein. This protein has a ubiquitin-binding zinc-finger domain in the N-terminus, an ATPase domain, and two leucine zipper motifs in the C-terminus. It has sequence similarity to replication factor C family proteins and is conserved from E. coli to human. This protein likely accumulates at sites of DNA damage by interacting with polyubiquinated proteins and also binds to DNA polymerase delta and increases the initiation frequency of DNA polymerase delta-mediated DNA synthesis. This protein also interacts with nucleoporins at nuclear pore complexes. Two transcript variants encoding different isoforms have been isolated for this gene.

Source: NCBI Gene 56897 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_020135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20876
Approved symbol	WRNIP1
Name	WRN helicase interacting protein 1
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	WHIP, FLJ22526, bA420G6.2, FAP93, CFAP93
Ensembl gene	ENSG00000124535
Ensembl biotype	protein_coding
OMIM	608196
Entrez	56897

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000380764, ENST00000380769, ENST00000380771, ENST00000380773, ENST00000618555, ENST00000922062, ENST00000922063

RefSeq mRNA: 2 — MANE Select: NM_020135 NM_020135, NM_130395

CCDS: CCDS4475, CCDS4476

Canonical transcript exons

ENST00000380773 — 7 exons

Exon	Start	End
ENSE00000847773	2784324	2784403
ENSE00001161213	2783406	2783561
ENSE00001161220	2779263	2779492
ENSE00001161232	2768691	2768882
ENSE00001486173	2785007	2786952
ENSE00003671041	2770120	2770361
ENSE00003892513	2765393	2766444

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.2545 / max 270.4276, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65457	24.6275	1806
65456	0.7357	414
65459	0.6797	365
65458	0.1978	70
65462	0.0139	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.04	gold quality
upper arm skin	UBERON:0004263	95.66	silver quality
medial globus pallidus	UBERON:0002477	95.20	gold quality
cerebellar hemisphere	UBERON:0002245	94.63	gold quality
cerebellar cortex	UBERON:0002129	94.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.35	gold quality
cerebellum	UBERON:0002037	94.33	gold quality
adenohypophysis	UBERON:0002196	94.24	gold quality
lower esophagus mucosa	UBERON:0035834	94.15	gold quality
globus pallidus	UBERON:0001875	94.06	gold quality
pituitary gland	UBERON:0000007	93.97	gold quality
ventricular zone	UBERON:0003053	93.81	gold quality
kidney epithelium	UBERON:0004819	93.79	silver quality
cerebellar vermis	UBERON:0004720	93.76	gold quality
body of pancreas	UBERON:0001150	93.71	gold quality
left ventricle myocardium	UBERON:0006566	93.69	silver quality
esophagus mucosa	UBERON:0002469	93.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.59	gold quality
prefrontal cortex	UBERON:0000451	93.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.42	gold quality
body of tongue	UBERON:0011876	93.40	gold quality
tibialis anterior	UBERON:0001385	93.39	silver quality
islet of Langerhans	UBERON:0000006	93.26	gold quality
pancreas	UBERON:0001264	93.08	gold quality
hypothalamus	UBERON:0001898	93.06	gold quality
minor salivary gland	UBERON:0001830	92.97	gold quality
anterior cingulate cortex	UBERON:0009835	92.91	gold quality
saliva-secreting gland	UBERON:0001044	92.85	gold quality
right coronary artery	UBERON:0001625	92.82	gold quality
ascending aorta	UBERON:0001496	92.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27
E-MTAB-6142	no	86.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting WRNIP1, 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-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-1912-5P	97.94	67.98	832

Literature-anchored findings (GeneRIF, showing 20)

• These results indicate that WRNIP1 functions as a modulator for initiation or restart events during pol delta-mediated DNA synthesis and that its ATPase activity is utilized to sense DNA ends and to regulate the extent of stimulation. (PMID:15670210)
• Werner helicase-interacting protein 1 binds polyubiquitin via its zinc finger domain (PMID:17550899)
• analysis of the composite and regulated topography of Wrnip1 in the human nucleus highlights its potential role in replication and other nuclear transactions (PMID:18842586)
• Data show that that WRNIP1 interacts physically with RAD18 and interferes with the binding of RAD18 to forked DNA and to template/primer DNA. (PMID:19556710)
• WHIP was identified as a partner/component of the nuclear envelope/nuclear pore complex (NPC) and set forth to investigate a role for the protein positioned at the NPC. (PMID:20676042)
• Mutated WRNIP1 with a deleted ATPase domain or with mutations in lysine residues accumulated in laser light irradiated sites, suggesting that the ATPase domain of WRNIP1 and ubiquitination of WRNIP1 are dispensable for the accumulation. (PMID:22209848)
• results suggest that WRNIP1 functions upstream of Poleta in the response to UV irradiation (PMID:25139235)
• WRNIP1 connects PCNA monoubiquitination with ATMIN/ATM to activate ATM signalling in response to replication stress and contribute to the maintenance of genomic stability. (PMID:26549024)
• We propose that UBZ domains can be divided into at least two different types in terms of the ubiquitin-binding surfaces: the pol type and the WRNIP1 type (PMID:27062441)
• The authors show that WRNIP1 is directly involved in preventing uncontrolled MRE11-mediated degradation of stalled replication forks by promoting RAD51 stabilization on ssDNA. (PMID:27242363)
• findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity. (PMID:29053956)
• The WRNIP1-mediated reduction in the amount of PrimPol was suppressed by treatment of the cells with proteasome inhibitors, suggesting that WRNIP1 is involved in the degradation of PrimPol via the proteasome. (PMID:31061318)
• miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1. (PMID:31190355)
• WRNIP1 Is Recruited to DNA Interstrand Crosslinks and Promotes Repair. (PMID:32640220)
• Functional Domain Mapping of Werner Interacting Protein 1 (WRNIP1). (PMID:35110507)
• R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1. (PMID:35163467)
• Discovering the nuclear localization signal of Werner Helicase Interacting Protein 1. (PMID:37268023)
• AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer. (PMID:38190717)
• WRNIP1 prevents transcription-associated genomic instability. (PMID:38488661)
• Werner helicase interacting protein 1 contributes to G-quadruplex processing in human cells. (PMID:38977862)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	wrnip1	ENSDARG00000005218
mus_musculus	Wrnip1	ENSMUSG00000021400
rattus_norvegicus	Wrnip1	ENSRNOG00000017040

Protein

Protein identifiers

ATPase WRNIP1 — Q96S55 (reviewed: Q96S55)

Alternative names: Werner helicase-interacting protein 1

All UniProt accessions (1): Q96S55

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a modulator of initiation or reinitiation events during DNA polymerase delta-mediated DNA synthesis. In the presence of ATP, stimulation of DNA polymerase delta-mediated DNA synthesis is decreased. Also plays a role in the innate immune defense against viruses. Stabilizes the RIGI dsRNA interaction and promotes RIGI ‘Lys-63’-linked polyubiquitination. In turn, RIGI transmits the signal through mitochondrial MAVS.

Subunit / interactions. Forms homooligomers, possibly octamers. Directly interacts with POLD1, POLD2 and POLD4. Interacts with the N-terminal domain of WRN. Interacts (via UBZ4-type zinc finger) with monoubiquitin and polyubiquitin. Interacts with TRIM14 and PPP6C; these interactions positively regulate the RIGI signaling pathway.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Sumoylated with SUMO1 and SUMO2/3.

Domain organisation. The UBZ4-type zinc finger binds ubiquitin.

Similarity. Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96S55-1	1	yes
Q96S55-2	2
Q96S55-3	3
Q96S55-4	4

RefSeq proteins (2): NP_064520, NP_569079 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR006642	Rad18_UBZ4	Domain
IPR008921	DNA_pol3_clamp-load_cplx_C	Homologous_superfamily
IPR021886	MgsA_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032423	AAA_assoc_2	Domain
IPR040539	Znf-WRNIP1_ubi	Domain
IPR051314	AAA_ATPase_RarA/MGS1/WRNIP1	Family

Pfam: PF00004, PF12002, PF16193, PF18279

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (65 total): cross-link 13, mutagenesis site 12, modified residue 11, sequence conflict 8, binding site 6, compositionally biased region 4, splice variant 3, strand 2, helix 2, chain 1, zinc finger region 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3VHS	X-RAY DIFFRACTION	1.9
3VHT	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S55-F1	72.68	0.41

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 (6): 35; 39; 270–276; 20; 23; 31

Post-translational modifications (24): 65, 75, 85, 91, 92, 116, 139, 153, 534, 562, 633, 81, 141, 225, 301, 310, 316, 322, 335, 482 …

Mutagenesis-validated functional residues (12):

Position	Phenotype
18	reduced affinity for ubiquitin.
21	loss of affinity for ubiquitin.
22	reduced affinity for ubiquitin.
32	loss of affinity for ubiquitin.
33	loss of affinity for ubiquitin.
36	loss of affinity for ubiquitin.
37	loss of affinity for ubiquitin.
40	loss of affinity for ubiquitin.
41	normal affinity for ubiquitin.
42	normal affinity for ubiquitin.
44	normal affinity for ubiquitin.
294	loss of atpase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, MODULE_255, MODULE_317, KAUFFMANN_DNA_REPAIR_GENES, chr6p25, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_BIOSYNTHETIC_PROCESS, GOBP_DNA_SYNTHESIS_INVOLVED_IN_DNA_REPAIR, GOBP_DNA_REPLICATION, GOCC_CHROMOSOMAL_REGION, MODULE_69, GOCC_CHROMOSOME_TELOMERIC_REGION, CAGCTTT_MIR320

GO Biological Process (9): DNA synthesis involved in DNA repair (GO:0000731), DNA-templated DNA replication (GO:0006261), regulation of DNA-templated DNA replication initiation (GO:0030174), innate immune response (GO:0045087), immune system process (GO:0002376), DNA replication (GO:0006260), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974)

GO Molecular Function (12): DNA binding (GO:0003677), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), single-stranded DNA helicase activity (GO:0017116), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515), four-way junction helicase activity (GO:0009378), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471), chromosome, telomeric region (GO:0000781), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
cellular anatomical structure	3
DNA biosynthetic process	2
catalytic activity	2
DNA helicase activity	2
DNA repair	1
DNA replication	1
DNA replication initiation	1
regulation of DNA-templated DNA replication	1
immune response	1
defense response to symbiont	1
biological_process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
chromosomal region	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WRNIP1	WRN	Q14191	996
WRNIP1	RAD18	Q9NS91	709
WRNIP1	ZRANB3	Q5FWF4	658
WRNIP1	FBH1	Q8NFZ0	619
WRNIP1	RECQL	P46063	610
WRNIP1	BOD1L1	Q8NFC6	598
WRNIP1	DNA2	P51530	596
WRNIP1	CEP43	O95684	581
WRNIP1	MUS81	Q96NY9	572
WRNIP1	PRIMPOL	Q96LW4	548
WRNIP1	HLTF	Q14527	547
WRNIP1	ATMIN	O43313	544
WRNIP1	EXO1	Q9UQ84	540
WRNIP1	EXD2	Q9NVH0	523
WRNIP1	ATAD5	Q96QE3	500

IntAct

109 interactions, top by confidence:

A	B	Type	Score
RIGI	MAVS	psi-mi:“MI:0914”(association)	0.960
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
PIK3R3	PIK3CD	psi-mi:“MI:0914”(association)	0.800
ANKRD44	PPP6C	psi-mi:“MI:0914”(association)	0.790
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
TMEM171	B3GAT3	psi-mi:“MI:0914”(association)	0.530
TRIM10	WIZ	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
WRNIP1	WRNIP1	psi-mi:“MI:0915”(physical association)	0.520
TNF	WRNIP1	psi-mi:“MI:0915”(physical association)	0.500
TOLLIP	IRAK2	psi-mi:“MI:0914”(association)	0.500
RIGI	WRNIP1	psi-mi:“MI:0915”(physical association)	0.500
WRNIP1	TOLLIP	psi-mi:“MI:0915”(physical association)	0.500
WRNIP1	POLD1	psi-mi:“MI:0914”(association)	0.500
POLD1	WRNIP1	psi-mi:“MI:0915”(physical association)	0.500
POLD2	WRNIP1	psi-mi:“MI:0915”(physical association)	0.500
POLD4	WRNIP1	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
UBASH3B	CHUK	psi-mi:“MI:0914”(association)	0.460
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
HTR2A	WRNIP1	psi-mi:“MI:0915”(physical association)	0.400
HTR2B	WRNIP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (181): WRNIP1 (Affinity Capture-MS), UBC (Reconstituted Complex), WRNIP1 (Affinity Capture-MS), WRNIP1 (Two-hybrid), WRNIP1 (Affinity Capture-MS), WRNIP1 (Affinity Capture-MS), WRNIP1 (Affinity Capture-MS), WRNIP1 (Affinity Capture-MS), WRNIP1 (Proximity Label-MS), WRNIP1 (Affinity Capture-MS), WRNIP1 (Co-crystal Structure), WRNIP1 (Affinity Capture-Western), WRNIP1 (Affinity Capture-MS), WRNIP1 (Reconstituted Complex), WRNIP1 (Reconstituted Complex)

ESM2 similar proteins: A2XUN8, A2YQ56, A4QN59, A5WVX1, A8MPP1, B8APQ0, B8AZ14, B9FKM7, D3ZG52, F1R345, O12944, O75417, P0C1Q3, P36776, P70270, P93648, Q01IJ3, Q07G10, Q0J7N5, Q10QS7, Q2VPA6, Q3UZW7, Q3V384, Q566Y1, Q59HJ6, Q69UZ3, Q6AXC6, Q6NTR1, Q6PH52, Q6ZQJ5, Q7X745, Q7XK25, Q8BFT6, Q8CG07, Q8CGK3, Q8CGS6, Q8GWT4, Q8H1F9, Q8N159, Q8R4H7

Diamond homologs: A1AC21, A1ARF8, A1KU52, A2C563, A5EXH6, A5G9Y2, A5IC73, A5N206, A6QC28, A7ZMY4, A8A160, A8FUX0, A8H545, A9LZC3, A9WHF8, B0SUN9, B0TF70, B0TSA7, B1J0M8, B1KGX9, B1XHC8, B2SYK2, B2TMZ2, B2UFL1, B3CMH5, B4RLV8, B5EAH3, B5YKE9, B5YR05, B7L7R3, B7M2F1, B7MBR9, B7MVZ1, B7NS58, B7USN7, B8CNY1, B8H454, B9E5Q8, B9KDF4, B9LBR4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
TNFR1-induced NF-kappa-B signaling pathway	5	17.0×	1e-03
Ovarian tumor domain proteases	6	16.9×	8e-04
Negative regulators of DDX58/IFIH1 signaling	5	16.5×	1e-03
NOD1/2 Signaling Pathway	5	16.0×	1e-03
SARS-CoV-1 activates/modulates innate immune responses	5	13.7×	2e-03
Regulation of TNFR1 signaling	6	13.6×	1e-03
Regulation of PTEN stability and activity	5	9.3×	7e-03
Interleukin-1 signaling	7	8.8×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of interferon-alpha production	6	32.1×	3e-05
canonical NF-kappaB signal transduction	6	18.2×	4e-04
positive regulation of interferon-beta production	5	16.2×	2e-03
negative regulation of canonical NF-kappaB signal transduction	8	11.4×	3e-04
positive regulation of canonical NF-kappaB signal transduction	10	6.0×	2e-03
inflammatory response	13	4.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1101 predictions. Top by Δscore:

Variant	Effect	Δscore
6:2770358:CAGAG:C	donor_loss	1.0000
6:2770360:GA:G	donor_gain	1.0000
6:2770361:AGTA:A	donor_loss	1.0000
6:2770362:G:GG	donor_gain	1.0000
6:2770362:GTA:G	donor_loss	1.0000
6:2770363:TAAG:T	donor_loss	1.0000
6:2766442:AAGG:A	donor_loss	0.9900
6:2766445:G:GC	donor_loss	0.9900
6:2766445:G:GG	donor_gain	0.9900
6:2766446:T:A	donor_loss	0.9900
6:2768690:GACCA:G	acceptor_gain	0.9900
6:2768878:AGCAG:A	donor_loss	0.9900
6:2768880:CAG:C	donor_loss	0.9900
6:2768881:AG:A	donor_loss	0.9900
6:2768882:G:GT	donor_loss	0.9900
6:2768883:G:T	donor_loss	0.9900
6:2768884:T:C	donor_loss	0.9900
6:2770358:CAGA:C	donor_gain	0.9900
6:2770359:AGA:A	donor_gain	0.9900
6:2770360:GAG:G	donor_gain	0.9900
6:2770364:A:AC	donor_loss	0.9900
6:2784321:CAGGT:C	acceptor_loss	0.9900
6:2784322:A:T	acceptor_loss	0.9900
6:2784400:TGAGG:T	donor_loss	0.9900
6:2784402:AGGT:A	donor_loss	0.9900
6:2784404:G:GA	donor_loss	0.9900
6:2784405:T:A	donor_loss	0.9900
6:2785001:TGGTA:T	acceptor_loss	0.9900
6:2785002:GGTA:G	acceptor_loss	0.9900
6:2785003:GTAG:G	acceptor_loss	0.9900

AlphaMissense

4365 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:2765680:T:C	C20R	1.000
6:2768851:A:T	D328V	1.000
6:2768863:G:C	R332P	1.000
6:2768881:A:C	Q338P	1.000
6:2768882:G:C	Q338H	1.000
6:2768882:G:T	Q338H	1.000
6:2770130:T:C	L342P	1.000
6:2770189:T:C	F362L	1.000
6:2770191:C:A	F362L	1.000
6:2770191:C:G	F362L	1.000
6:2770205:C:A	A367D	1.000
6:2765680:T:A	C20S	0.999
6:2765681:G:C	C20S	0.999
6:2766421:T:A	W267R	0.999
6:2766421:T:C	W267R	0.999
6:2766424:G:A	G268R	0.999
6:2766424:G:C	G268R	0.999
6:2766425:G:A	G268E	0.999
6:2766434:G:A	G271D	0.999
6:2766440:G:A	G273D	0.999
6:2766440:G:T	G273V	0.999
6:2768701:C:A	A278D	0.999
6:2768758:C:A	A297E	0.999
6:2768802:G:C	A312P	0.999
6:2768803:C:A	A312D	0.999
6:2768842:T:C	L325P	0.999
6:2768850:G:C	D328H	0.999
6:2768851:A:C	D328A	0.999
6:2768853:G:A	E329K	0.999
6:2768854:A:C	E329A	0.999

dbSNP variants (sampled 300 via entrez): RS1000054432 (6:2778922 A>G,T), RS1000097558 (6:2787262 A>G), RS1000108001 (6:2779187 T>C,G), RS1000180073 (6:2772684 T>A,G), RS1000585993 (6:2765439 G>A), RS1000789991 (6:2779721 T>C,G), RS1000843002 (6:2786665 G>A), RS1000897009 (6:2786898 A>G), RS1000921175 (6:2765313 T>C,G), RS1001000656 (6:2768374 A>T), RS1001005793 (6:2782599 G>A,T), RS1001050179 (6:2768614 G>A,C), RS1001158865 (6:2765585 T>A), RS1001309290 (6:2763800 TGA>T,TGAGA), RS1001355011 (6:2782468 C>T)

Disease associations

OMIM: gene MIM:608196 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002400_659	Plateletcrit	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methotrexate	increases expression	1
Ozone	affects cotreatment, decreases expression	1
Phthalic Acids	increases methylation	1
Quercetin	increases phosphorylation	1
Rotenone	decreases expression	1
Smoke	increases abundance, increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7X2	SEES3-1V human WRNIP1, clone1	Embryonic stem cell	Male
CVCL_A7X3	SEES3-1V human WRNIP1, clone2	Embryonic stem cell	Male
CVCL_A7X4	SEES3-1V human WRNIP1, clone3	Embryonic stem cell	Male
CVCL_B2LH	Abcam HeLa WRNIP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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