GINS1

Summary

GINS1 (GINS complex subunit 1, HGNC:28980) is a protein-coding gene on chromosome 20p11.21, encoding DNA replication complex GINS protein PSF1 (Q14691). Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The yeast heterotetrameric GINS complex is made up of Sld5 (GINS4; MIM 610611), Psf1, Psf2 (GINS2; MIM 610609), and Psf3 (GINS3; MIM 610610). The formation of the GINS complex is essential for the initiation of DNA replication in yeast and Xenopus egg extracts (Ueno et al., 2005 [PubMed 16287864]).

Source: NCBI Gene 9837 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to GINS1 deficiency (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 208 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 18
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_021067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28980
Approved symbol	GINS1
Name	GINS complex subunit 1
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0186, PSF1
Ensembl gene	ENSG00000101003
Ensembl biotype	protein_coding
OMIM	610608
Entrez	9837

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 10 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000262460, ENST00000473460, ENST00000481735, ENST00000484893, ENST00000696793, ENST00000696798, ENST00000696803, ENST00000696804, ENST00000696805, ENST00000696806, ENST00000696807, ENST00000696808, ENST00000696810, ENST00000696813, ENST00000696814, ENST00000696862, ENST00000696870, ENST00000696874, ENST00000696875, ENST00000696876, ENST00000696877, ENST00000696878, ENST00000696894, ENST00000696895, ENST00000696896

RefSeq mRNA: 3 — MANE Select: NM_021067 NM_001410830, NM_001410831, NM_021067

CCDS: CCDS33451, CCDS93022, CCDS93023

Canonical transcript exons

ENST00000262460 — 7 exons

Exon	Start	End
ENSE00001825970	25407673	25407895
ENSE00003469730	25413790	25413854
ENSE00003629964	25441702	25441776
ENSE00003659236	25425211	25425327
ENSE00003968490	25418105	25418195
ENSE00003968491	25417104	25417202
ENSE00003968492	25445923	25448563

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 97.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3251 / max 230.9802, expressed in 1477 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183935	14.3251	1477

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.17	gold quality
secondary oocyte	CL:0000655	95.70	gold quality
sperm	CL:0000019	93.41	gold quality
endometrium epithelium	UBERON:0004811	90.69	gold quality
male germ cell	CL:0000015	90.57	gold quality
cervix squamous epithelium	UBERON:0006922	88.49	silver quality
embryo	UBERON:0000922	87.80	gold quality
ventricular zone	UBERON:0003053	87.67	gold quality
esophagus squamous epithelium	UBERON:0006920	85.47	gold quality
right testis	UBERON:0004534	85.40	gold quality
left testis	UBERON:0004533	84.79	gold quality
testis	UBERON:0000473	84.15	gold quality
squamous epithelium	UBERON:0006914	83.87	gold quality
ganglionic eminence	UBERON:0004023	83.79	gold quality
endothelial cell	CL:0000115	83.14	gold quality
epithelium of esophagus	UBERON:0001976	82.73	gold quality
trabecular bone tissue	UBERON:0002483	79.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.66	gold quality
gingival epithelium	UBERON:0001949	78.84	gold quality
thymus	UBERON:0002370	78.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.21	gold quality
adult organism	UBERON:0007023	78.11	gold quality
bone marrow	UBERON:0002371	77.77	gold quality
gingiva	UBERON:0001828	77.32	gold quality
oral cavity	UBERON:0000167	77.22	gold quality
hair follicle	UBERON:0002073	77.07	silver quality
oviduct epithelium	UBERON:0004804	76.15	gold quality
mucosa of transverse colon	UBERON:0004991	76.11	gold quality
mucosa of sigmoid colon	UBERON:0004993	75.66	gold quality
upper leg skin	UBERON:0004262	75.60	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	115.18
E-MTAB-6678	yes	7.93
E-ANND-3	yes	5.25
E-MTAB-6911	no	297.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, E2F4

miRNA regulators (miRDB)

87 targeting GINS1, 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-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-767-5P	99.95	70.85	993
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4306	99.72	70.50	3630
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

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 17)

• expression of mammalian GINS is regulated by 17beta-Estradiol-stimulated estrogen receptor alpha, and PSF3 acts as a gene responsive to transcription factor E2F1 (PMID:17127213)
• the C-terminal domain of Psf1 does not contribute to the stability of the GINS complex but is crucial for chromatin binding and replication activity (PMID:17417653)
• Findings implicate PSF1 in tumorigenesis and offer initial evidence of its potential as a theranostic target. (PMID:20103637)
• These results suggest that PSF1 over-expression is specifically involved in breast cancer cell growth. (PMID:20825491)
• PSF1 mRNA expression was an independent factor associated with prognosis of colorectal cancer. (PMID:21713706)
• The authors show that GINS is a compact tetramer in solution as observed in crystal structures, but also forms a double-tetrameric population, detectable by electron microscopy. (PMID:28071757)
• Autosomal recessive, partial GINS1 deficiency impairs DNA replication and underlies intra-uterine (and postnatal) growth retardation, chronic neutropenia, and NK cell deficiency. (PMID:28414293)
• mRNA expressions of all GINS subunits were significantly up-regulated in hepatocellular carcinoma tumor than in non-tumor liver tissues. (PMID:30413605)
• High GINS1 expression is associated with reactivation of quiescent stem-like tumor cells within the peri-necrotic niche in glioblastoma. (PMID:30465075)
• MALAT1 modulated FOXP3 ubiquitination then affected GINS1 transcription and drived NSCLC proliferation. (PMID:33972684)
• Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer. (PMID:34852135)
• Combined analysis of expression, prognosis and immune infiltration of GINS family genes in human sarcoma. (PMID:35896011)
• A Novel Tumor-Promoting Role for Nuclear Factor IX in Glioblastoma Is Mediated through Transcriptional Activation of GINS1. (PMID:36469009)
• Transcription Factor E2F1 Enhances Hepatocellular Carcinoma Cell Proliferation and Stemness by Activating GINS1. (PMID:37824372)
• GINS1 promotes ZEB1-mediated epithelial-mesenchymal transition and tumor metastasis via beta-catenin signaling in hepatocellular carcinoma. (PMID:38468464)
• GINS1 promotes the initiation and progression of bladder cancer by activating the AKT/mTOR/c-Myc signaling pathway. (PMID:38880324)
• OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) modulates the stemness feature, chemoresistance, and epithelial-mesenchymal transition of colon cancer via regulating GINS complex subunit 1 (GINS1) expression. (PMID:39210373)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gins1	ENSDARG00000007624
mus_musculus	Gins1	ENSMUSG00000027454
rattus_norvegicus	Gins1	ENSRNOG00000008091
drosophila_melanogaster	Psf1	FBGN0035194
caenorhabditis_elegans		WBGENE00011275

Protein

Protein identifiers

DNA replication complex GINS protein PSF1 — Q14691 (reviewed: Q14691)

Alternative names: GINS complex subunit 1

All UniProt accessions (15): Q14691, A0A8Q3SIW3, A0A8Q3SIY5, A0A8Q3SJ10, A0A8Q3SJ38, A0A8Q3SJK6, A0A8Q3WLJ3, A0A8Q3WLK7, A0A8Q3WLL0, A0A8Q3WLL7, A0A8Q3WLM7, A0A8Q3WLP3, A0A8Q3WM37, A0A8Q3WMG9, A0A8Q3WMM5

UniProt curated annotations — full annotation on UniProt →

Function. Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built.

Subunit / interactions. Component of the GINS complex which is a heterotetramer of GINS1, GINS2, GINS3 and GINS4. Forms a stable subcomplex with GINS4. GINS complex interacts with DNA primase in vitro. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex.

Subcellular location. Nucleus. Chromosome.

Disease relevance. Immunodeficiency 55 (IMD55) [MIM:617827] An autosomal recessive primary immunodeficiency characterized by chronic neutropenia, natural killer cell deficiency, recurrent viral and bacterial infections, and intrauterine growth retardation. Postnatal growth retardation is present in most patients. The disease is caused by variants affecting the gene represented in this entry.

Induction. Significantly up-regulated in aggressive melanomas.

Similarity. Belongs to the GINS1/PSF1 family.

RefSeq proteins (3): NP_001397759, NP_001397760, NP_066545* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005339	GINS_Psf1	Family
IPR021151	GINS_A	Domain
IPR036224	GINS_bundle-like_dom_sf	Homologous_superfamily
IPR056783	PSF1_C	Domain

Pfam: PF05916, PF24997

UniProt features (12 total): helix 6, sequence variant 3, strand 2, chain 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2E9X	X-RAY DIFFRACTION	2.3
2Q9Q	X-RAY DIFFRACTION	2.36
9E2Z	ELECTRON MICROSCOPY	2.6
7PLO	ELECTRON MICROSCOPY	2.8
2EHO	X-RAY DIFFRACTION	3
7PFO	ELECTRON MICROSCOPY	3.2
6XTX	ELECTRON MICROSCOPY	3.29
8B9D	ELECTRON MICROSCOPY	3.4
8OK2	ELECTRON MICROSCOPY	4.1
6XTY	ELECTRON MICROSCOPY	6.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14691-F1	93.26	0.78

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-176974	Unwinding of DNA

MSigDB gene sets: 339 (showing top): REACTOME_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GNF2_MSH2, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, KANG_DOXORUBICIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELL_CYCLE_DNA_REPLICATION, CROONQUIST_NRAS_SIGNALING_DN, GOBP_DNA_STRAND_ELONGATION_INVOLVED_IN_DNA_REPLICATION, GOBP_GROWTH, MITSIADES_RESPONSE_TO_APLIDIN_DN, GENTILE_RESPONSE_CLUSTER_D3, GNF2_MCM5, GNF2_RRM1, SHEPARD_BMYB_MORPHOLINO_DN

GO Biological Process (3): inner cell mass cell proliferation (GO:0001833), DNA replication (GO:0006260), DNA strand elongation involved in mitotic DNA replication (GO:1902983)

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

GO Cellular Component (6): GINS complex (GO:0000811), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), CMG complex (GO:0071162), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA strand elongation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear chromosome	2
DNA replication preinitiation complex	2
cellular anatomical structure	2
blastocyst growth	1
cell population proliferation	1
DNA metabolic process	1
DNA biosynthetic process	1
DNA strand elongation involved in nuclear cell cycle DNA replication	1
mitotic DNA replication	1
mitotic cell cycle process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
GINS complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GINS1	GINS4	Q9BRT9	999
GINS1	GINS3	Q9BRX5	999
GINS1	GINS2	Q9Y248	998
GINS1	CDC45	O75419	932
GINS1	MCM10	Q7L590	855
GINS1	MCM5	P33992	834
GINS1	MCM3	P25205	803
GINS1	MCM4	P33991	780
GINS1	MCM7	P33993	752
GINS1	MCM2	P49736	702
GINS1	POLE2	P56282	666
GINS1	MCM6	Q14566	592
GINS1	DBF4	Q9UBU7	582
GINS1	TOP2A	P11388	576
GINS1	NCAPG2	Q86XI2	557

IntAct

46 interactions, top by confidence:

A	B	Type	Score
GINS3	GINS1	psi-mi:“MI:0914”(association)	0.880
GINS1	GINS4	psi-mi:“MI:0915”(physical association)	0.860
GINS1	GINS4	psi-mi:“MI:0914”(association)	0.860
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
GINS1	CDC45	psi-mi:“MI:0914”(association)	0.620
GINS1	CDC45	psi-mi:“MI:0915”(physical association)	0.620
GINS1	DONSON	psi-mi:“MI:2364”(proximity)	0.580
DONSON	GINS1	psi-mi:“MI:0915”(physical association)	0.580
MCM7	CEP290	psi-mi:“MI:0914”(association)	0.530
GINS3	MCM7	psi-mi:“MI:0914”(association)	0.530
CSNK1G2	GINS1	psi-mi:“MI:0914”(association)	0.530
CENATAC	GINS1	psi-mi:“MI:0914”(association)	0.530
PTP4A1	ATE1	psi-mi:“MI:0914”(association)	0.530
MCM7	VPS26A	psi-mi:“MI:0914”(association)	0.530
DONSON	CDC45	psi-mi:“MI:0914”(association)	0.500
	SCO2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (77): GINS1 (Two-hybrid), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-MS), GINS1 (Co-fractionation), GINS1 (Co-fractionation), GINS4 (Co-fractionation), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-MS), GINS1 (Reconstituted Complex), GINS1 (Affinity Capture-MS), GINS1 (Affinity Capture-Western)

ESM2 similar proteins: A2VE40, A4IFH4, G5EDN3, O94329, P0CQ30, P29458, P41229, P41230, P52590, P57740, P91133, Q03406, Q09915, Q12488, Q14691, Q22019, Q2HE71, Q2KI89, Q38JA7, Q499W2, Q54HR6, Q55EA2, Q5R629, Q626F4, Q6BXX6, Q6BZ44, Q6CE80, Q6CHE4, Q6CKF3, Q6CPV6, Q6CRT8, Q6CW43, Q6FS76, Q6FT85, Q6FVY5, Q6NQP5, Q753I0, Q75E92, Q7ZT47, Q7ZT48

Diamond homologs: A4IFH4, Q14691, Q22019, Q54HR6, Q59S42, Q626F4, Q7ZT47, Q9CZ15, Q9P7X6, P0CQ28, P0CQ29, Q0UN58, Q12488, Q2HDQ7, Q4IP51, Q5B714, Q6BKI2, Q6CHE4, Q6CW43, Q6FVY5, Q75E92, Q7SDH9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
YAP1	“up-regulates quantity by expression”	GINS1	“transcriptional regulation”
YAP/TAZ	“up-regulates quantity by expression”	GINS1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Synthesis of DNA	6	78.4×	4e-09
Activation of the pre-replicative complex	5	70.9×	1e-07
DNA Replication Pre-Initiation	5	69.0×	1e-07
Activation of ATR in response to replication stress	5	65.3×	2e-07
DNA Replication	6	62.1×	1e-08
G1/S Transition	5	50.7×	5e-07
S Phase	6	47.3×	5e-08
Mitotic G1 phase and G1/S transition	5	40.0×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
DNA replication initiation	5	91.8×	1e-07
DNA replication	9	43.7×	4e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	128
Likely benign	59
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2423575	NC_000020.10:g.(?25319843)(25426627_?)del	Pathogenic
487513	NM_021067.5(GINS1):c.455G>A (p.Cys152Tyr)	Likely pathogenic

SpliceAI

1267 predictions. Top by Δscore:

Variant	Effect	Δscore
20:25407896:G:GG	donor_gain	1.0000
20:25417089:A:AG	acceptor_gain	1.0000
20:25417089:AAAT:A	acceptor_gain	1.0000
20:25417090:A:G	acceptor_gain	1.0000
20:25417092:T:G	acceptor_gain	1.0000
20:25417198:TACCT:T	donor_gain	1.0000
20:25417203:G:GG	donor_gain	1.0000
20:25418193:GAA:G	donor_gain	1.0000
20:25418196:G:GG	donor_gain	1.0000
20:25425325:G:GT	donor_gain	1.0000
20:25425325:GAA:G	donor_gain	1.0000
20:25425328:G:GG	donor_gain	1.0000
20:25441696:TTTCA:T	acceptor_loss	1.0000
20:25441697:TTCA:T	acceptor_loss	1.0000
20:25441698:TCA:T	acceptor_loss	1.0000
20:25441699:CAGGT:C	acceptor_loss	1.0000
20:25441700:A:AC	acceptor_loss	1.0000
20:25441700:A:AG	acceptor_gain	1.0000
20:25441701:G:GA	acceptor_gain	1.0000
20:25407872:G:GT	donor_gain	0.9900
20:25407878:C:T	donor_gain	0.9900
20:25407902:G:T	donor_gain	0.9900
20:25413853:GT:G	donor_gain	0.9900
20:25413855:G:GG	donor_gain	0.9900
20:25417090:AAT:A	acceptor_gain	0.9900
20:25417091:A:AG	acceptor_gain	0.9900
20:25417091:AT:A	acceptor_gain	0.9900
20:25417092:T:TA	acceptor_gain	0.9900
20:25417171:T:G	donor_gain	0.9900
20:25417199:ACCT:A	donor_gain	0.9900

AlphaMissense

1268 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:25441760:T:C	L169S	0.999
20:25425217:T:A	W113R	0.997
20:25425217:T:C	W113R	0.997
20:25441710:T:G	C152W	0.997
20:25417157:G:C	R65P	0.996
20:25418112:C:A	R83S	0.996
20:25418113:G:C	R83P	0.996
20:25417169:T:C	L69P	0.995
20:25441706:G:C	R151P	0.995
20:25445972:T:C	L191P	0.995
20:25417184:G:C	R74P	0.994
20:25418141:G:C	W92C	0.994
20:25418141:G:T	W92C	0.994
20:25441703:T:A	V150D	0.994
20:25441708:T:C	C152R	0.994
20:25445930:T:C	L177S	0.994
20:25445946:T:G	C182W	0.994
20:25445957:T:A	I186N	0.994
20:25418139:T:A	W92R	0.993
20:25418139:T:C	W92R	0.993
20:25425242:T:C	L121P	0.993
20:25441709:G:A	C152Y	0.993
20:25445944:T:C	C182R	0.992
20:25445972:T:A	L191Q	0.992
20:25445945:G:A	C182Y	0.991
20:25413843:C:A	N43K	0.990
20:25413843:C:G	N43K	0.990
20:25417198:T:G	Y79D	0.990
20:25418112:C:G	R83G	0.990
20:25425305:C:A	P142Q	0.990

dbSNP variants (sampled 300 via entrez): RS1000008557 (20:25444550 T>C), RS1000049933 (20:25408509 G>A), RS1000126464 (20:25409350 T>C), RS1000281365 (20:25431988 C>T), RS1000308380 (20:25425439 C>T), RS1000352907 (20:25437265 A>G), RS1000376691 (20:25431684 C>T), RS1000522082 (20:25426534 CT>C,CTT), RS1000549642 (20:25427185 G>A,C,T), RS1000601773 (20:25414279 A>ATCTGC), RS1000615485 (20:25433066 G>T), RS1000616386 (20:25425906 T>C), RS1000708635 (20:25432808 T>C), RS1000749525 (20:25432513 A>G), RS1000778624 (20:25439886 T>C)

Disease associations

OMIM: gene MIM:610608 | disease phenotypes: MIM:617827

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency due to GINS1 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
combined immunodeficiency due to GINS1 deficiency	Moderate	AR

Mondo (1): combined immunodeficiency due to GINS1 deficiency (MONDO:0044725)

Orphanet (1): Combined immunodeficiency due to GINS1 deficiency (Orphanet:505227)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0001511	Intrauterine growth retardation
HP:0001581	Recurrent skin infections
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count
HP:0001999	Abnormal facial shape
HP:0002014	Diarrhea
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002863	Myelodysplasia
HP:0004322	Short stature
HP:0008064	Ichthyosis
HP:0008897	Postnatal growth retardation
HP:0034197	Third trimester onset
HP:0040219	Absent natural killer cells

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001276_7	Liver enzyme levels (alkaline phosphatase)	7.000000e-10
GCST006485_13	Telomere length	1.000000e-06
GCST010703_48	Brain morphology (MOSTest)	1.000000e-08
GCST90002402_585	Platelet count	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0004346	neuroimaging measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	6
bisphenol A	affects expression, decreases expression, increases expression	4
Cyclosporine	decreases expression	4
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
propionaldehyde	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
methylparaben	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
periodate-oxidized adenosine	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
polyhexamethyleneguanidine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
oligofectamine	increases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1

Clinical trials (associated diseases)

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