PMS1

Summary

PMS1 (PMS1 homolog 1, mismatch repair system component, HGNC:9121) is a protein-coding gene on chromosome 2q32.2, encoding PMS1 protein homolog 1 (P54277). Probably involved in the repair of mismatches in DNA.

This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome.

Source: NCBI Gene 5378 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lynch syndrome (Refuted, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 182 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 63
• MANE Select transcript: NM_000534

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9121
Approved symbol	PMS1
Name	PMS1 homolog 1, mismatch repair system component
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Aliases	MLH2
Ensembl gene	ENSG00000064933
Ensembl biotype	protein_coding
OMIM	600258
Entrez	5378

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 42 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000342075, ENST00000374826, ENST00000409593, ENST00000409823, ENST00000409985, ENST00000418224, ENST00000420421, ENST00000421722, ENST00000424059, ENST00000424307, ENST00000424766, ENST00000432292, ENST00000441310, ENST00000446877, ENST00000447232, ENST00000447734, ENST00000450931, ENST00000452382, ENST00000483293, ENST00000618056, ENST00000624204, ENST00000899827, ENST00000899828, ENST00000899829, ENST00000899830, ENST00000899831, ENST00000899832, ENST00000899833, ENST00000899834, ENST00000921100, ENST00000921101, ENST00000921102, ENST00000921103, ENST00000921104, ENST00000921105, ENST00000921106, ENST00000921107, ENST00000921108, ENST00000921109, ENST00000921110, ENST00000921111, ENST00000921112, ENST00000921113, ENST00000921114, ENST00000921115, ENST00000961090, ENST00000961091, ENST00000961092

RefSeq mRNA: 12 — MANE Select: NM_000534 NM_000534, NM_001128143, NM_001128144, NM_001289408, NM_001289409, NM_001321044, NM_001321045, NM_001321046, NM_001321047, NM_001321048, NM_001321049, NM_001321051

CCDS: CCDS2302, CCDS46473, CCDS46474, CCDS74615, CCDS82543, CCDS82544

Canonical transcript exons

ENST00000441310 — 13 exons

Exon	Start	End
ENSE00003510516	189853939	189854082
ENSE00003558243	189854239	189855128
ENSE00003580698	189852655	189852777
ENSE00003594300	189843964	189844080
ENSE00003610607	189818017	189818180
ENSE00003612746	189805652	189805754
ENSE00003627883	189867799	189867929
ENSE00003635116	189863743	189864228
ENSE00003662411	189795769	189795951
ENSE00003790937	189873496	189873656
ENSE00003800278	189791790	189791941
ENSE00003900570	189877272	189877629
ENSE00003901442	189784450	189784593

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8368 / max 201.7010, expressed in 1764 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24258	11.0699	1725
202511	1.7115	919
24259	0.0316	4
24260	0.0174	4
24261	0.0065	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.45	gold quality
male germ cell	CL:0000015	97.93	gold quality
left testis	UBERON:0004533	95.13	gold quality
right testis	UBERON:0004534	94.94	gold quality
oocyte	CL:0000023	94.40	gold quality
testis	UBERON:0000473	94.04	gold quality
endothelial cell	CL:0000115	92.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.53	gold quality
calcaneal tendon	UBERON:0003701	91.79	gold quality
secondary oocyte	CL:0000655	91.66	gold quality
tibia	UBERON:0000979	90.22	gold quality
ventricular zone	UBERON:0003053	89.86	gold quality
choroid plexus epithelium	UBERON:0003911	89.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.43	gold quality
epithelium of nasopharynx	UBERON:0001951	89.20	gold quality
tendon	UBERON:0000043	88.72	gold quality
embryo	UBERON:0000922	88.58	gold quality
endometrium	UBERON:0001295	88.58	gold quality
skin of hip	UBERON:0001554	88.34	gold quality
right uterine tube	UBERON:0001302	88.18	gold quality
ganglionic eminence	UBERON:0004023	87.89	gold quality
bronchial epithelial cell	CL:0002328	87.62	gold quality
seminal vesicle	UBERON:0000998	87.40	gold quality
caput epididymis	UBERON:0004358	87.13	gold quality
parietal pleura	UBERON:0002400	87.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.04	gold quality
pleura	UBERON:0000977	86.98	gold quality
visceral pleura	UBERON:0002401	86.84	gold quality
upper leg skin	UBERON:0004262	86.79	gold quality
adrenal tissue	UBERON:0018303	86.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.34
E-MTAB-7606	no	412.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting PMS1, 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-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243

Literature-anchored findings (GeneRIF, showing 11)

• hMutSalpha forms an ATP-dependent complex with hMutLalpha and hMutLbeta on DNA (PMID:11809883)
• The expression of hMLH1 and hPMS1 was significantly low in some large B-cell lymphomas and in mantle cell lymphomas of the blastoid type and may be related to the natural history of these neoplasms. (PMID:11999575)
• Data show that DNA damage induces the accumulation of hPMS1, hPMS2, and hMLH1 through ataxia-telangiectasia-mutated (ATM)-mediated protein stabilization. (PMID:15226443)
• hPMS1 may be useful as CD4+ helper T cell antigens for immunotherapy of pancreatic cancer patients. (PMID:15856462)
• In pstreplicative mismatch repair, this protein interacts wiwth MutL protein. (PMID:17148452)
• PMS1 is most likely deregulated by post-transcriptional modification in oral squamous cell carcinoma. (PMID:23608172)
• These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway. (PMID:24204293)
• Genome-wide association study identifies variants in PMS1 associated with serum ferritin in a Chinese population. (PMID:25162662)
• Study suggests that rs1233255 SNP in PMS1 is associated with acute adverse events (AEs), and three SNPs, including rs4920657, rs5743030 and rs5743100 in PMS1, are associated with survival of rectal cancer patients receiving postoperative chemoradiotherapy (CRT). Therefore, these polymorphisms may be potential independent biomarkers for predicting AEs and prognosis in rectal cancer patients receiving postoperative CRT. (PMID:30590005)
• Analysis of the MLH1, MLH2, MLH6, PMS2 genes and their correlations with clinical data in rectal mucinous adenocarcinoma. (PMID:34807001)
• Investigation of discordant sibling pairs from hereditary breast cancer families and analysis of a rare PMS1 variant. (PMID:34852986)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pms1	ENSDARG00000000476
mus_musculus	Pms1	ENSMUSG00000026098
rattus_norvegicus	Pms1	ENSRNOG00000004076

Paralogs (3): MLH1 (ENSG00000076242), MLH3 (ENSG00000119684), PMS2 (ENSG00000122512)

Protein

Protein identifiers

PMS1 protein homolog 1 — P54277 (reviewed: P54277)

Alternative names: DNA mismatch repair protein PMS1

All UniProt accessions (14): P54277, B7ZAA0, C9J4L1, C9JF76, C9JKP0, E9PC40, E9PC65, E9PH88, F8W8L1, Q3BDU3, Q5FBZ4, Q5FBZ7, Q5FBZ9, Q5XG96

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in the repair of mismatches in DNA.

Subunit / interactions. Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. The MutL-beta complex is a heterodimer of PMS1 and MLH1. Interacts with MCM9.

Subcellular location. Nucleus.

Similarity. Belongs to the DNA mismatch repair MutL/HexB family.

Isoforms (4)

UniProt ID	Names	Canonical?
P54277-1	1	yes
P54277-2	2
P54277-3	3
P54277-4	4

RefSeq proteins (12): NP_000525, NP_001121615, NP_001121616, NP_001276337, NP_001276338, NP_001307973, NP_001307974, NP_001307975, NP_001307976, NP_001307977, NP_001307978, NP_001307980 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002099	MutL/Mlh/PMS	Family
IPR009071	HMG_box_dom	Domain
IPR013507	DNA_mismatch_S5_2-like	Domain
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR014762	DNA_mismatch_repair_CS	Conserved_site
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR038973	MutL/Mlh/Pms-like	Family

Pfam: PF00505, PF01119, PF13589

UniProt features (19 total): sequence variant 7, helix 4, splice variant 4, chain 1, DNA-binding region 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CS1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54277-F1	70.02	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): mismatch repair (GO:0006298), response to xenobiotic stimulus (GO:0009410), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (7): DNA binding (GO:0003677), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), mismatched DNA binding (GO:0030983), ATP-dependent DNA damage sensor activity (GO:0140664), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), MutLalpha complex (GO:0032389), mismatch repair complex (GO:0032300)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	1
response to chemical	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein binding	1
double-stranded DNA binding	1
ATP-dependent activity, acting on DNA	1
DNA damage sensor activity	1
binding	1
intracellular membrane-bounded organelle	1
mismatch repair complex	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

2040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PMS1	MSH2	P43246	999
PMS1	MSH6	P52701	998
PMS1	MSH3	P20585	995
PMS1	MLH1	P40692	993
PMS1	MLH3	P49751	979
PMS1	PMS2	P54278	974
PMS1	EXO1	Q9UQ84	896
PMS1	FAN1	Q9Y2M0	827
PMS1	MUTYH	Q9UIF7	813
PMS1	MSH4	O15457	809
PMS1	MSH5	O43196	794
PMS1	POLD1	P28340	759
PMS1	BRCA1	P38398	753
PMS1	EPCAM	P16422	699
PMS1	ATM	Q13315	692

IntAct

62 interactions, top by confidence:

A	B	Type	Score
BRIP1	MLH1	psi-mi:“MI:0914”(association)	0.940
MLH1	PMS1	psi-mi:“MI:0915”(physical association)	0.830
MLH1	PMS1	psi-mi:“MI:0914”(association)	0.830
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
MLH1	HSPA8	psi-mi:“MI:0914”(association)	0.500
MCM9	MSH3	psi-mi:“MI:0914”(association)	0.460
PMS1	LTF	psi-mi:“MI:0915”(physical association)	0.400
PMS1		psi-mi:“MI:0915”(physical association)	0.370
ECE1	PMS1	psi-mi:“MI:0915”(physical association)	0.370
SNX21	POLR1G	psi-mi:“MI:0914”(association)	0.350
BBS7	PER1	psi-mi:“MI:0914”(association)	0.350
PMS1	HRAS	psi-mi:“MI:0914”(association)	0.350
FRMD6		psi-mi:“MI:0914”(association)	0.350
MCM9	NOP56	psi-mi:“MI:0914”(association)	0.350
MCM9	PSMD14	psi-mi:“MI:0914”(association)	0.350
FAN1	MLH1	psi-mi:“MI:0914”(association)	0.350
FSCN1	FANCG	psi-mi:“MI:0914”(association)	0.350
FSCN1	UBB	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
BBS7	TARS3	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350

BioGRID (136): PMS1 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), PMS1 (Proximity Label-MS), PMS1 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), HIST1H1D (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), PMS1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), AHNAK (Affinity Capture-MS), VAMP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8J1LLF7, A1KXW8, A6QL50, B0K012, B3DLA6, E1BGQ2, H0Y354, O94955, P42694, P47224, P54277, P57060, Q08326, Q1A730, Q1JQA1, Q1RMS8, Q1RMZ1, Q2KHT6, Q3T0J1, Q4R372, Q4R528, Q504Q3, Q5F480, Q5R9U9, Q5RCQ0, Q5RDU9, Q5RFG8, Q5TYM5, Q5ZLS2, Q641X7, Q6DFV5, Q6IE70, Q6L9T8, Q7SXV1, Q7Z6J8, Q86X60, Q8BFZ8, Q8BGF7, Q8BX13, Q8N5C7

Diamond homologs: A1KUP6, A2RP08, A3CR14, A4D2B8, A5D2K5, A5EXM6, A5F3L5, A6QGJ5, A6U1B5, A7HC45, A7X1T8, A8AZU1, A8F560, A8MQ11, A8Z1W7, A9BJB9, A9M0G1, A9MFP2, B0K1A3, B0K9L6, B0R2S6, B0RRZ8, B0SB85, B0ST13, B0TB10, B0U5C6, B1H0C7, B2I9E6, B2IYW1, B2KB18, B2SHP8, B2VCU8, B3PDC3, B4F203, B4RLX4, B5F385, B7LLV2, B8D891, B8D8D4, B8DFS3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PMS1	“form complex”	MLH1/PMS1	binding
PMS1	“up-regulates activity”	DNA_repair

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	101
Likely benign	19
Benign	24

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
152531	GRCh38/hg38 2q32.2(chr2:189828954-189853926)x1	Pathogenic
998151	NM_000534.5(PMS1):c.2766del (p.His923fs)	Pathogenic
135042	NM_000534.5(PMS1):c.287C>G (p.Ala96Gly)	Likely pathogenic
2445388	NM_000534.5(PMS1):c.2780A>G (p.Tyr927Cys)	Likely pathogenic
4277551	NM_000534.5(PMS1):c.237_238del (p.Asn79fs)	Likely pathogenic
4845637	NM_000534.5(PMS1):c.58del (p.Ser20fs)	Likely pathogenic

SpliceAI

3038 predictions. Top by Δscore:

Variant	Effect	Δscore
2:189785426:G:GT	donor_gain	1.0000
2:189785467:GATTT:G	donor_gain	1.0000
2:189785472:G:GG	donor_gain	1.0000
2:189791785:TCTA:T	acceptor_loss	1.0000
2:189791786:CTAG:C	acceptor_loss	1.0000
2:189791787:TA:T	acceptor_loss	1.0000
2:189791788:A:AC	acceptor_loss	1.0000
2:189791788:A:AG	acceptor_gain	1.0000
2:189791788:AGCT:A	acceptor_gain	1.0000
2:189791789:G:GT	acceptor_gain	1.0000
2:189791789:GC:G	acceptor_gain	1.0000
2:189791789:GCT:G	acceptor_gain	1.0000
2:189791789:GCTG:G	acceptor_gain	1.0000
2:189791789:GCTGC:G	acceptor_gain	1.0000
2:189791938:ACTG:A	donor_gain	1.0000
2:189791938:ACTGG:A	donor_loss	1.0000
2:189791939:CTG:C	donor_gain	1.0000
2:189791940:TG:T	donor_gain	1.0000
2:189791940:TGG:T	donor_loss	1.0000
2:189791941:GG:G	donor_gain	1.0000
2:189791941:GGTG:G	donor_loss	1.0000
2:189791942:G:GG	donor_gain	1.0000
2:189791943:TGAGT:T	donor_loss	1.0000
2:189791944:GAGT:G	donor_loss	1.0000
2:189795763:TTATA:T	acceptor_loss	1.0000
2:189795764:TATA:T	acceptor_loss	1.0000
2:189805750:TCAAG:T	donor_loss	1.0000
2:189805751:CAAGG:C	donor_loss	1.0000
2:189805752:AAGGT:A	donor_loss	1.0000
2:189805753:AGGTA:A	donor_loss	1.0000

AlphaMissense

6217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:189795779:G:A	G48E	0.999
2:189795910:T:C	F92L	0.999
2:189795912:T:A	F92L	0.999
2:189795912:T:G	F92L	0.999
2:189791892:T:C	L28P	0.998
2:189818063:A:C	R155S	0.998
2:189818063:A:T	R155S	0.998
2:189854057:A:T	K314I	0.998
2:189791940:T:C	L44P	0.997
2:189795802:G:C	D56H	0.997
2:189795911:T:C	F92S	0.997
2:189818062:G:C	R155T	0.997
2:189852749:G:C	R265P	0.997
2:189791934:T:A	V42D	0.996
2:189795778:G:A	G48R	0.996
2:189795778:G:C	G48R	0.996
2:189795800:G:C	R55P	0.996
2:189795914:G:C	R93P	0.996
2:189795946:G:C	A104P	0.996
2:189805688:A:C	S118R	0.996
2:189805690:C:A	S118R	0.996
2:189805690:C:G	S118R	0.996
2:189852727:A:C	S258R	0.996
2:189852729:T:A	S258R	0.996
2:189852729:T:G	S258R	0.996
2:189852748:C:G	R265G	0.996
2:189867909:T:C	F818S	0.996
2:189873629:A:C	R869S	0.996
2:189873629:A:T	R869S	0.996
2:189877278:G:C	A881P	0.996

dbSNP variants (sampled 300 via entrez): RS1000010479 (2:189849372 A>G), RS1000020936 (2:189796567 T>C), RS1000031957 (2:189815702 G>A,C), RS1000062186 (2:189860960 C>A,T), RS1000119983 (2:189869036 A>T), RS1000186803 (2:189812240 G>A), RS1000212054 (2:189821903 T>C), RS1000220876 (2:189812493 A>G), RS1000290595 (2:189875399 A>G), RS1000301697 (2:189829312 T>C), RS1000302528 (2:189809765 G>A), RS1000377268 (2:189785935 G>A,C), RS1000468321 (2:189863248 T>G), RS1000480057 (2:189792127 A>G), RS1000527496 (2:189810961 A>C)

Disease associations

OMIM: gene MIM:600258 | disease phenotypes: MIM:120435, MIM:167000, MIM:614337, MIM:114500

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Lynch syndrome	Refuted	AD

Mondo (7): Lynch syndrome 1 (MONDO:0007356), ovarian cancer (MONDO:0008170), hereditary breast ovarian cancer syndrome (MONDO:0003582), Lynch syndrome (MONDO:0005835), Lynch syndrome 4 (MONDO:0013699), polyp of colon (MONDO:0021400), colorectal cancer (MONDO:0005575)

Orphanet (4): Lynch syndrome (Orphanet:144), Rare ovarian cancer (Orphanet:213500), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

63 total (30 of 63 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000505	Visual impairment
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0001123	Visual field defect
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001371	Flexion contracture
HP:0001402	Hepatocellular carcinoma
HP:0001522	Death in infancy
HP:0001824	Weight loss
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002076	Migraine
HP:0002167	Abnormal speech pattern
HP:0002239	Gastrointestinal hemorrhage
HP:0002354	Memory impairment
HP:0002376	Developmental regression
HP:0002516	Increased intracranial pressure
HP:0002671	Basal cell carcinoma
HP:0002893	Pituitary adenoma
HP:0002894	Neoplasm of the pancreas

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001521_21	Subcutaneous adipose tissue	5.000000e-06
GCST001762_565	Obesity-related traits	6.000000e-06
GCST002578_1	Ferritin levels	2.000000e-10
GCST004573_3	Iron status biomarkers (ferritin levels)	2.000000e-07
GCST006866_1	Lung cancer (SNP x SNP interaction)	1.000000e-13
GCST012485_13	Cerebral amyloid angiopathy x sex interaction in Alzheimer’s disease	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004459	ferritin measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D003111	Colonic Polyps	C23.300.825.411.235
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
C563971	Colorectal Cancer, Hereditary Nonpolyposis, Type 4 (supp.)
C537261	Lynch syndrome I (site-specific colonic cancer) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5742933	ORMDL1, PMS1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	6
Tetrachlorodibenzodioxin	decreases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
sodium arsenite	affects methylation, decreases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
pradimicin-IRD	affects expression, affects response to substance	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric oxide	decreases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
O(6)-benzylguanine	affects cotreatment, affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
riccardin D	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	affects cotreatment, affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5KP	HAP1 PMS1 (-) 2	Cancer cell line	Male
CVCL_XR68	HAP1 PMS1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer