PMS2

Summary

PMS2 (PMS1 homolog 2, mismatch repair system component, HGNC:9122) is a protein-coding gene on chromosome 7p22.1, encoding Mismatch repair endonuclease PMS2 (P54278). Component of the post-replicative DNA mismatch repair system (MMR). In precision oncology, PMS2 K706FS*19 confers sensitivity to Nivolumab in Glioblastoma (CIViC Level C). It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome.

Source: NCBI Gene 5395 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lynch syndrome (Definitive, ClinGen) — +10 more curated relationships
• Clinical variants (ClinVar): 6,094 total — 745 pathogenic, 165 likely-pathogenic
• Phenotypes (HPO): 71
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9122
Approved symbol	PMS2
Name	PMS1 homolog 2, mismatch repair system component
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	H_DJ0042M02.9, HNPCC4, MLH4, PMS-2
Ensembl gene	ENSG00000122512
Ensembl biotype	protein_coding
OMIM	600259
Entrez	5395

Gene structure

Transcript identifiers

Ensembl transcripts: 72 — 36 nonsense_mediated_decay, 23 protein_coding, 9 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000265849, ENST00000382321, ENST00000406569, ENST00000415839, ENST00000469652, ENST00000642292, ENST00000642456, ENST00000643595, ENST00000644110, ENST00000699752, ENST00000699753, ENST00000699754, ENST00000699755, ENST00000699756, ENST00000699757, ENST00000699758, ENST00000699759, ENST00000699760, ENST00000699761, ENST00000699762, ENST00000699763, ENST00000699764, ENST00000699765, ENST00000699766, ENST00000699767, ENST00000699768, ENST00000699769, ENST00000699770, ENST00000699811, ENST00000699813, ENST00000699814, ENST00000699815, ENST00000699816, ENST00000699817, ENST00000699818, ENST00000699819, ENST00000699820, ENST00000699821, ENST00000699822, ENST00000699823, ENST00000699824, ENST00000699825, ENST00000699826, ENST00000699827, ENST00000699828, ENST00000699829, ENST00000699830, ENST00000699831, ENST00000699832, ENST00000699833, ENST00000699834, ENST00000699837, ENST00000699838, ENST00000699839, ENST00000699840, ENST00000699916, ENST00000699917, ENST00000699918, ENST00000699919, ENST00000699920, ENST00000699928, ENST00000699929, ENST00000699930, ENST00000699931, ENST00000699932, ENST00000699933, ENST00000699951, ENST00000699952, ENST00000699953, ENST00000699954, ENST00000703409, ENST00000933314

RefSeq mRNA: 60 — MANE Select: NM_000535 NM_000535, NM_001322003, NM_001322004, NM_001322005, NM_001322006, NM_001322007, NM_001322008, NM_001322009, NM_001322010, NM_001322011, NM_001322012, NM_001322013, NM_001322014, NM_001322015, NM_001406866, NM_001406868, NM_001406869, NM_001406870, NM_001406871, NM_001406872, NM_001406873, NM_001406874, NM_001406875, NM_001406876, NM_001406877, NM_001406878, NM_001406879, NM_001406880, NM_001406881, NM_001406882, NM_001406883, NM_001406884, NM_001406885, NM_001406886, NM_001406887, NM_001406888, NM_001406889, NM_001406890, NM_001406891, NM_001406892, NM_001406893, NM_001406894, NM_001406895, NM_001406896, NM_001406897, NM_001406898, NM_001406899, NM_001406900, NM_001406901, NM_001406902, NM_001406903, NM_001406904, NM_001406905, NM_001406906, NM_001406907, NM_001406908, NM_001406909, NM_001406910, NM_001406911, NM_001406912

CCDS: CCDS5343, CCDS83155, CCDS87474, CCDS94048, CCDS94049, CCDS94050, CCDS94051, CCDS94052

Canonical transcript exons

ENST00000265849 — 15 exons

Exon	Start	End
ENSE00000669421	5986759	5987620
ENSE00001608691	5977588	5977757
ENSE00001752874	5982824	5982991
ENSE00001793579	5978596	5978696
ENSE00001848021	6008997	6009049
ENSE00001848489	5970925	5973542
ENSE00003478459	6003690	6003792
ENSE00003610845	6005892	6006031
ENSE00003684470	6003972	6004058
ENSE00003713592	5997326	5997423
ENSE00003715574	6002453	6002636
ENSE00003732666	5989800	5989955
ENSE00003734436	5995534	5995633
ENSE00003739198	5999108	5999275
ENSE00003739851	5991973	5992057

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 86.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6122 / max 66.4794, expressed in 1657 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82621	4.2069	1599
82622	1.4053	793

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	86.50	silver quality
prefrontal cortex	UBERON:0000451	83.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.56	gold quality
superior frontal gyrus	UBERON:0002661	83.28	gold quality
cortical plate	UBERON:0005343	82.56	gold quality
frontal cortex	UBERON:0001870	82.45	gold quality
corpus callosum	UBERON:0002336	82.30	gold quality
endometrium	UBERON:0001295	81.80	gold quality
stromal cell of endometrium	CL:0002255	81.71	gold quality
ventricular zone	UBERON:0003053	81.71	gold quality
cerebellar cortex	UBERON:0002129	81.53	gold quality
cerebellar hemisphere	UBERON:0002245	81.51	gold quality
cerebellum	UBERON:0002037	81.50	gold quality
cerebral cortex	UBERON:0000956	81.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.10	gold quality
tonsil	UBERON:0002372	81.09	gold quality
primary visual cortex	UBERON:0002436	81.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.98	gold quality
skin of abdomen	UBERON:0001416	80.69	gold quality
zone of skin	UBERON:0000014	80.62	gold quality
adrenal tissue	UBERON:0018303	80.58	gold quality
adult mammalian kidney	UBERON:0000082	80.57	gold quality
embryo	UBERON:0000922	80.44	gold quality
ganglionic eminence	UBERON:0004023	80.44	gold quality
skin of leg	UBERON:0001511	80.43	gold quality
right frontal lobe	UBERON:0002810	80.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.33	gold quality
kidney	UBERON:0002113	80.31	gold quality
anterior cingulate cortex	UBERON:0009835	80.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHE41, MYC, RBAK, TP53

miRNA regulators (miRDB)

72 targeting PMS2, 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-4455	100.00	65.48	1587
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms in HNPCC (PMID:11793469)
• hMutSalpha forms an ATP-dependent complex with hMutLalpha and hMutLbeta on DNA (PMID:11809883)
• Contribution of human mlh1 and pms2 ATPase activities to DNA mismatch repair. (PMID:11897781)
• Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalpha (PMID:11948175)
• PMS2 contributes to genome integrity not only through DNA repair but also by enhancing DNA damage-induced apoptosis (PMID:12601175)
• Mutations of this protein show microsatellite instability in human prostatic cancer (PMID:12684669)
• hPMS2 accounts for a small proportion of Hereditary non-polyposis colorectal cancer families, and none were deemed to be associated with hEXO1 (PMID:14756672)
• PMS2 may have a role in hereditary nonpolyposis colorectal cancer (PMID:14871975)
• PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome (PMID:15077197)
• Data show that DNA damage induces the accumulation of hPMS1, hPMS2, and hMLH1 through ataxia-telangiectasia-mutated (ATM)-mediated protein stabilization. (PMID:15226443)
• PMS2 defects account for a small but significant proportion of colorectal cancers and for a substantial fraction of tumors with microsatellite instability (PMID:15887099)
• Mutation results in a distinct autosomal recessive cancer predisposition syndrome. (PMID:16042583)
• Loss of expression of PMS2 was associated with young age of diagnosis and right-sided location but not with a striking family history of cancer. (PMID:16166421)
• biochemical analysis of the MutLalpha. MutSalpha complex (PMID:16403449)
• Heterozygous truncating mutations in PMS2 do play a role in a small subset of patients with Lynch syndrome, indicated a need for mutational analysis. (PMID:16472587)
• information on the phenotype associated with PMS2 mutations in childhood cancer in 13 patients from six families of Pakistani origin living in the United Kingdom (PMID:16507833)
• PMS2 rs7797466 may have a role in development of ovarian cancer (PMID:16774946)
• In primary breast cancers we found that the hPMS2 gene had 9 missense mutations. (PMID:17016615)
• results strongly suggest that hPMS2-E705K is a recessive loss-of-function allele (PMID:17029773)
• PMS2 elevation is a prognostic marker in pre-neoplastic and prostate cancer lesions. (PMID:17044039)
• In pstreplicative mismatch repair, this protein interacts wiwth MutL protein. (PMID:17148452)
• Expression of hMSH2 and hMLH1 proteins was up-regulated in three cases, whereas in two cases that of hPMS2 was increased. hMSH6 expression was comparable to that of normal cells in all cases. (PMID:17493242)
• gene conversion has been suggested to be a mutation mechanism underlying PMS2 inactivation, this is the first report of its involvement in a pathogenic mutation (PMID:17557300)
• predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1 (PMID:17581638)
• The researchers found evidence of a large genomic deletion of exons 1-10 in the PMS2 gene associated with the clinical phenotype of Lynch syndrome. (PMID:17653898)
• provide further evidence for childhood cancer syndrome in six children from two consanguineous families carrying homozygous PMS2 germline mutations (PMID:17851451)
• A homozygous complex MSH6 splicing alteration in the index patients of the first family and a novel homozygous PMS2 mutation (c.182delA) in the index patient of the second family, were identified. (PMID:18030674)
• A frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients, is identified. (PMID:18178629)
• Adenine nucleotides induce large asymmetric conformational changes in full-length human MutL alpha. These changes are associated with significant increases in secondary structure. (PMID:18206974)
• new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by cafe-au-lait macules, colonic polyps and a distinctive tumor spectrum (PMID:18273873)
• The role of RBaK, PMS2, and GNA12 in the inheritance of familial hyperaldosteronism type II were studied. (PMID:18307725)
• A consanguineous Australian-Lebanese family with multiple affected individuals shown to be homozygous for a PMS2 exon 7 deletion. (PMID:18376293)
• PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. (PMID:18602922)
• Data suggest that MutLalpha is a zinc ion binding protein and confirm this prediction by way of biochemical analysis of zinc ion binding using the full-length and C-terminal domain of MutLalpha. (PMID:18619468)
• PMS2(R20Q) lacks proapoptotic activity, this polymorphic allele may modulate tumor responses to cisplatin among cancer patients (PMID:18768816)
• PMS2 plays a role in class switch recombination-induced double-strand DNA break generation. (PMID:18824584)
• study identified 4 patients with a pathogenic PMS2 mutation (4%) among the 97 Lynch syndrome-suspected patients selected; study confirms the finding of previous studies that PMS2 is more frequently involved in Lynch syndrome than originally expected (PMID:19132747)
• data indicate that hPMS2 is more protective of tetranucleotide expansions than deletions and that hPMS2 displays a sequence bias, wherein [TTCC/AAGG] sequences are stabilized to a greater extent than [TTTC/AAAG]. (PMID:19155293)
• Case report: Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer. (PMID:19479271)
• MutLalpha (MLH1-PMS2), replication protein A (RPA), and HMGB1 have roles in 5’-directed mismatch repair (PMID:19515846)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pms2	ENSDARG00000075672
mus_musculus	Pms2	ENSMUSG00000079109
rattus_norvegicus	Pms2	ENSRNOG00000001040
drosophila_melanogaster	Pms2	FBGN0011660
caenorhabditis_elegans		WBGENE00004064

Paralogs (3): PMS1 (ENSG00000064933), MLH1 (ENSG00000076242), MLH3 (ENSG00000119684)

Protein

Protein identifiers

Mismatch repair endonuclease PMS2 — P54278 (reviewed: P54278)

Alternative names: DNA mismatch repair protein PMS2, PMS1 protein homolog 2

All UniProt accessions (37): A0A2R8Y6S3, A0A8V8TNQ7, A0A8V8TNR3, A0A8V8TNR7, A0A8V8TNV6, A0A8V8TNW1, A0A8V8TNX1, A0A8V8TNX6, A0A8V8TNY8, A0A8V8TNZ8, A0A8V8TP55, A0A8V8TP61, A0A8V8TP66, A0A8V8TP72, A0A8V8TP79, A0A8V8TP84, A0A8V8TP89, A0A8V8TPD1, A0A8V8TPE1, A0A8V8TPE7, A0A8V8TPJ6, A0A8V8TPK2, A0A8V8TQ41, A0A8V8TQ50, A0A8V8TQ88, A0A8V8TQ92, A0A8V8TQG9, A0A8V8TQH3, A0A8V8TQH7, A0A8V8TQI1, A0A8V8TQM5, A0A8V8TQN0, A0A8V8TQR6, A0A8V8TQS5, A0A8V8TQT4, C9J167, P54278

UniProt curated annotations — full annotation on UniProt →

Function. Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Possesses an ATPase activity, but in the absence of gross structural changes, ATP hydrolysis may not be necessary for proficient mismatch repair.

Subunit / interactions. Heterodimer of PMS2 and MLH1 (MutL alpha); this interaction is required for the stability of both partners. Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MTMR15/FAN1.

Subcellular location. Nucleus.

Disease relevance. Lynch syndrome 4 (LYNCH4) [MIM:614337] A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term ‘suspected Lynch syndrome’ or ‘incomplete Lynch syndrome’ can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. The disease is caused by variants affecting the gene represented in this entry. Mismatch repair cancer syndrome 4 (MMRCS4) [MIM:619101] An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P54278-1	1	yes
P54278-2	2
P54278-3	3
P54278-4	4

RefSeq proteins (60): NP_000526, NP_001308932, NP_001308933, NP_001308934, NP_001308935, NP_001308936, NP_001308937, NP_001308938, NP_001308939, NP_001308940, NP_001308941, NP_001308942, NP_001308943, NP_001308944, NP_001393795, NP_001393797, NP_001393798, NP_001393799, NP_001393800, NP_001393801, NP_001393802, NP_001393803, NP_001393804, NP_001393805, NP_001393806, NP_001393807, NP_001393808, NP_001393809, NP_001393810, NP_001393811, NP_001393812, NP_001393813, NP_001393814, NP_001393815, NP_001393816, NP_001393817, NP_001393818, NP_001393819, NP_001393820, NP_001393821, NP_001393822, NP_001393823, NP_001393824, NP_001393825, NP_001393826, NP_001393827, NP_001393828, NP_001393829, NP_001393830, NP_001393831, NP_001393832, NP_001393833, NP_001393834, NP_001393835, NP_001393836, NP_001393837, NP_001393838, NP_001393839, NP_001393840, NP_001393841 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002099	MutL/Mlh/PMS	Family
IPR013507	DNA_mismatch_S5_2-like	Domain
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR014762	DNA_mismatch_repair_CS	Conserved_site
IPR014790	MutL_C	Domain
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR037198	MutL_C_sf	Homologous_superfamily
IPR038973	MutL/Mlh/Pms-like	Family
IPR042120	MutL_C_dimsub	Homologous_superfamily
IPR042121	MutL_C_regsub	Homologous_superfamily

Pfam: PF01119, PF08676, PF13589

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (112 total): sequence variant 54, strand 18, helix 13, binding site 5, splice variant 5, mutagenesis site 5, compositionally biased region 4, turn 3, modified residue 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
1H7S	X-RAY DIFFRACTION	1.95
7RCB	X-RAY DIFFRACTION	2
9S89	X-RAY DIFFRACTION	2
7RCK	X-RAY DIFFRACTION	2.04
5U5R	X-RAY DIFFRACTION	2.1
7RCI	X-RAY DIFFRACTION	2.12
6MFQ	X-RAY DIFFRACTION	2.6
1EA6	X-RAY DIFFRACTION	2.7
1H7U	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54278-F1	71.37	0.36

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 (5): 110; 111; 45; 70; 109

Post-translational modifications (2): 573, 597

Mutagenesis-validated functional residues (5):

Position	Phenotype
41	decreased dna mismatch repair activity; loss of atpase activity.
70	no effect on protein abundance, no effect on subcellular localization and loss of dna mismatch repair activity.
519	no effect on dna mismatch repair activity.
577	affects binding to importins alpha, including kpna2, hence may affect import to the nucleus.
578	affects binding to importins alpha, including kpna2, hence may affect import to the nucleus.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5545483	Defective Mismatch Repair Associated With MLH1
R-HSA-5632987	Defective Mismatch Repair Associated With PMS2
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes

MSigDB gene sets: 0 (showing top):

GO Biological Process (8): mismatch repair (GO:0006298), response to xenobiotic stimulus (GO:0009410), somatic hypermutation of immunoglobulin genes (GO:0016446), somatic recombination of immunoglobulin gene segments (GO:0016447), positive regulation of isotype switching to IgA isotypes (GO:0048298), positive regulation of isotype switching to IgG isotypes (GO:0048304), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (13): DNA binding (GO:0003677), endonuclease activity (GO:0004519), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), single base insertion or deletion binding (GO:0032138), ATP-dependent DNA damage sensor activity (GO:0140664), nucleotide binding (GO:0000166), single-stranded DNA binding (GO:0003697), nuclease activity (GO:0004518), protein binding (GO:0005515), hydrolase activity (GO:0016787), mismatched DNA binding (GO:0030983), MutSalpha complex binding (GO:0032407)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), MutLalpha complex (GO:0032389), mismatch repair complex (GO:0032300)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mismatch Repair	2
Diseases of Mismatch Repair (MMR)	2
Transcriptional Regulation by TP53	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
somatic diversification of immunoglobulins	2
positive regulation of isotype switching	2
cellular anatomical structure	2
DNA repair	1
response to chemical	1
somatic diversification of immune receptors via somatic mutation	1
somatic diversification of immune receptors via germline recombination within a single locus	1
isotype switching to IgA isotypes	1
regulation of isotype switching to IgA isotypes	1
isotype switching to IgG isotypes	1
regulation of isotype switching to IgG isotypes	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
nuclease activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
DNA insertion or deletion binding	1
ATP-dependent activity, acting on DNA	1
DNA damage sensor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
DNA binding	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
double-stranded DNA binding	1
mismatch repair complex binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
mismatch repair complex	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

2416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PMS2	MSH2	P43246	999
PMS2	MSH6	P52701	999
PMS2	MSH3	P20585	998
PMS2	MLH1	P40692	993
PMS2	MLH3	P49751	979
PMS2	PMS1	P54277	974
PMS2	EXO1	Q9UQ84	972
PMS2	MUTYH	Q9UIF7	896
PMS2	BRCA2	P51587	876
PMS2	POLD1	P28340	872
PMS2	MSH5	O43196	871
PMS2	BRCA1	P38398	865
PMS2	EPCAM	P16422	864
PMS2	POLE	Q07864	850
PMS2	BRAF	P15056	834

IntAct

88 interactions, top by confidence:

A	B	Type	Score
BRIP1	BRCA1	psi-mi:“MI:0914”(association)	0.980
PMS2	MLH1	psi-mi:“MI:0407”(direct interaction)	0.970
MLH1	PMS2	psi-mi:“MI:0915”(physical association)	0.970
PMS2	MLH1	psi-mi:“MI:0915”(physical association)	0.970
MLH1	PMS2	psi-mi:“MI:0914”(association)	0.970
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
FSCN1	MLH1	psi-mi:“MI:0914”(association)	0.600
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530

BioGRID (154): PMS2 (Affinity Capture-MS), PMS2 (Co-fractionation), PMS2 (Proximity Label-MS), PMS2 (Reconstituted Complex), ABCA2 (Affinity Capture-MS), FYN (Affinity Capture-MS), MLH1 (Affinity Capture-MS), PMS2 (Affinity Capture-MS), PMS2 (Affinity Capture-MS), PMS2 (Affinity Capture-MS), PMS2 (Affinity Capture-MS), FAN1 (Affinity Capture-MS), ZNRD1 (Affinity Capture-MS), BRIP1 (Affinity Capture-MS), PMS2 (Affinity Capture-MS)

ESM2 similar proteins: A4IHS0, A5WUX7, B5XAM2, D2HD32, D6WIX5, O44568, P10711, P23193, P30775, P41767, P52652, P54278, P54279, P82673, Q09691, Q12322, Q14197, Q16VC0, Q29RL9, Q2YDF6, Q3T116, Q3UFY8, Q497V5, Q498P2, Q4KLL0, Q5D892, Q5RDI0, Q5U2R4, Q5U2X7, Q63799, Q6DCC6, Q6NW52, Q7JUX9, Q80VP5, Q8BJZ4, Q8C1Z8, Q8CCM6, Q8K2Y7, Q8MT06, Q8N5C6

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

3 interactions.

A	Effect	B	Mechanism
TP53	“up-regulates quantity”	PMS2	“transcriptional regulation”
PMS2	“form complex”	MLH1/PMS2	binding
PMS2	“up-regulates activity”	DNA_repair

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
HDR through Homologous Recombination (HRR)	5	24.4×	5e-04
TP53 Regulates Transcription of DNA Repair Genes	5	23.2×	5e-04
PKR-mediated signaling	6	21.7×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	5	36.8×	9e-05
DNA repair	9	11.1×	8e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: ambiguous (mixed evidence) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

6094 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	745
Likely pathogenic	165
Uncertain significance	2779
Likely benign	925
Benign	162

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1048958	NM_000535.7(PMS2):c.1145-982_2006+2del	Pathogenic
1049209	NM_000535.7(PMS2):c.989-1_1144+2del	Pathogenic
1049246	NM_000535.7(PMS2):c.2276-1_2445+2del	Pathogenic
1049418	NM_000535.7(PMS2):c.368del (p.Ser123fs)	Pathogenic
1049466	NM_000535.7(PMS2):c.2446-170_*3del	Pathogenic
1049610	NM_000535.7(PMS2):c.1145-1_2006+2del	Pathogenic
1049762	NM_000535.7(PMS2):c.2445+1763_*2del	Pathogenic
1049801	NM_000535.7(PMS2):c.2492_2493del (p.Ile831fs)	Pathogenic
1049913	NM_000535.7(PMS2):c.804-267_903+2del	Pathogenic
1050117	NM_000535.7(PMS2):c.2445+1601_*3del	Pathogenic
1050329	NM_000535.7(PMS2):c.2175-1335_2445+4del	Pathogenic
1050469	NM_000535.7(PMS2):c.904-199_988+2del	Pathogenic
1050527	NM_000535.7(PMS2):c.2446-440_*2del	Pathogenic
1050621	NM_000535.7(PMS2):c.538-41_538-40insATTCCTATAATA	Pathogenic
1068580	NM_000535.7(PMS2):c.130G>T (p.Glu44Ter)	Pathogenic
1068638	NM_000535.7(PMS2):c.673G>T (p.Glu225Ter)	Pathogenic
1068755	NM_000535.7(PMS2):c.2179C>T (p.Gln727Ter)	Pathogenic
1068868	NC_000007.13:g.(?6022445)(6022632_?)del	Pathogenic
1068869	NC_000007.13:g.(?6022449)(6022628_?)del	Pathogenic
1068926	NM_000535.7(PMS2):c.2208del (p.Ala737fs)	Pathogenic
1069161	NC_000007.13:g.(?_6013020)_6031698del	Pathogenic
1069789	NM_000535.7(PMS2):c.1159del (p.Met387fs)	Pathogenic
1069911	NM_000535.7(PMS2):c.42del (p.Ile15fs)	Pathogenic
1071163	NC_000007.13:g.(?6026380)(6043699_?)del	Pathogenic
1071164	NC_000007.13:g.(?6035155)(6043699_?)del	Pathogenic
1071165	NC_000007.13:g.(?6026380)(6038916_?)del	Pathogenic
1071219	NM_000535.7(PMS2):c.451dup (p.Arg151fs)	Pathogenic
1072973	NC_000007.13:g.(?6013030)(6017398_?)del	Pathogenic
1073413	NM_000535.7(PMS2):c.543T>G (p.Tyr181Ter)	Pathogenic
1074077	NM_000535.7(PMS2):c.735dup (p.Pro246fs)	Pathogenic

SpliceAI

3037 predictions. Top by Δscore:

Variant	Effect	Δscore
7:5977582:ACTT:A	donor_loss	1.0000
7:5977584:TTAC:T	donor_loss	1.0000
7:5977586:A:AC	donor_gain	1.0000
7:5977586:A:C	donor_loss	1.0000
7:5977587:C:CG	donor_gain	1.0000
7:5977587:CCGA:C	donor_gain	1.0000
7:5977715:C:CC	acceptor_gain	1.0000
7:5977758:C:CC	acceptor_gain	1.0000
7:5978590:ACTT:A	donor_loss	1.0000
7:5978591:CTTA:C	donor_loss	1.0000
7:5978592:TTA:T	donor_loss	1.0000
7:5978593:T:TG	donor_loss	1.0000
7:5978594:A:AT	donor_loss	1.0000
7:5978694:GGT:G	acceptor_gain	1.0000
7:5978695:GT:G	acceptor_gain	1.0000
7:5978696:TCTGA:T	acceptor_loss	1.0000
7:5978697:C:CC	acceptor_gain	1.0000
7:5978697:CTGA:C	acceptor_loss	1.0000
7:5982820:TCA:T	donor_loss	1.0000
7:5982821:CACGC:C	donor_loss	1.0000
7:5982822:A:AC	donor_gain	1.0000
7:5982823:C:CC	donor_gain	1.0000
7:5982823:C:CT	donor_loss	1.0000
7:5982823:CG:C	donor_gain	1.0000
7:5982823:CGCT:C	donor_gain	1.0000
7:5982882:T:TA	donor_gain	1.0000
7:5982989:TTA:T	acceptor_gain	1.0000
7:5982992:C:CC	acceptor_gain	1.0000
7:5989794:TCTTA:T	donor_loss	1.0000
7:5989795:CTTAC:C	donor_loss	1.0000

AlphaMissense

5735 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:5973467:A:G	W841R	1.000
7:5973467:A:T	W841R	1.000
7:5982883:C:A	E705D	1.000
7:5982883:C:G	E705D	1.000
7:5973435:T:A	R851S	0.999
7:5973435:T:G	R851S	0.999
7:5973447:C:A	R847S	0.999
7:5973447:C:G	R847S	0.999
7:5973448:C:G	R847T	0.999
7:5973461:A:G	C843R	0.999
7:5977676:A:G	L786P	0.999
7:5982884:T:A	E705V	0.999
7:5982902:T:A	D699V	0.999
7:5982902:T:G	D699A	0.999
7:5982940:A:C	F686L	0.999
7:5982940:A:T	F686L	0.999
7:5982942:A:G	F686L	0.999
7:5982944:C:T	G685E	0.999
7:5982945:C:G	G685R	0.999
7:5982945:C:T	G685R	0.999
7:5982953:A:G	F682S	0.999
7:5989925:T:A	K340I	0.999
7:6003725:A:C	F106L	0.999
7:6003725:A:T	F106L	0.999
7:6003727:A:G	F106L	0.999
7:5973436:C:G	R851T	0.998
7:5973448:C:A	R847M	0.998
7:5973449:T:C	R847G	0.998
7:5973459:A:C	C843W	0.998
7:5973465:C:A	W841C	0.998

dbSNP variants (sampled 300 via entrez): RS10000 (7:5973522 A>C,G), RS1000116954 (7:5994672 AG>A), RS1000306148 (7:6007636 A>G), RS1000311292 (7:5972460 C>T), RS1000430281 (7:5971577 T>C), RS1000567689 (7:5993551 T>C), RS1000598642 (7:6007921 A>ACGAT), RS1000801363 (7:6002972 A>C,T), RS1000803164 (7:5994219 A>C), RS1000871023 (7:5983348 A>T), RS1000923860 (7:5998883 G>A), RS1000946340 (7:5994093 T>C), RS1001072184 (7:5993824 G>A), RS1001130469 (7:5993983 A>G), RS1001131141 (7:6000664 A>G)

Disease associations

OMIM: gene MIM:600259 | disease phenotypes: MIM:614337, MIM:619101, MIM:120435, MIM:167000, MIM:276300, MIM:114480, MIM:613659, MIM:114550, MIM:614350, MIM:604370, MIM:612555, MIM:113970, MIM:604145, MIM:613765

GenCC curated gene-disease

Disease	Classification	Inheritance
Lynch syndrome	Definitive	Autosomal dominant
mismatch repair cancer syndrome 1	Definitive	Autosomal recessive
Lynch syndrome 4	Definitive	Autosomal dominant
mismatch repair cancer syndrome 4	Definitive	Autosomal recessive
rhabdomyosarcoma	Moderate	Autosomal recessive
Muir-Torre syndrome	Moderate	Autosomal recessive
ovarian cancer	Moderate	Autosomal dominant
malignant pancreatic neoplasm	Moderate	Autosomal dominant
breast cancer	Limited	Autosomal dominant
prostate cancer	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
Lynch syndrome	Definitive	AD
hereditary breast carcinoma	Disputed	AD
mismatch repair cancer syndrome 1	Definitive	AR

Mondo (36): Lynch syndrome (MONDO:0005835), Lynch syndrome 4 (MONDO:0013699), hereditary neoplastic syndrome (MONDO:0015356), mismatch repair cancer syndrome 4 (MONDO:0030843), breast cancer (MONDO:0007254), endometrial carcinoma (MONDO:0002447), colon carcinoma (MONDO:0002032), hereditary nonpolyposis colon cancer (MONDO:0018630), breast carcinoma (MONDO:0004989), hereditary breast ovarian cancer syndrome (MONDO:0003582), ovarian cancer (MONDO:0008170), mismatch repair cancer syndrome 1 (MONDO:0010159), hereditary breast carcinoma (MONDO:0016419), Lynch syndrome 1 (MONDO:0007356), cancer or benign tumor (MONDO:0045024)

Orphanet (14): Inherited cancer-predisposing syndrome (Orphanet:140162), Lynch syndrome (Orphanet:144), Hereditary nonpolyposis colon cancer (Orphanet:443909), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Rare ovarian cancer (Orphanet:213500), Constitutional mismatch repair deficiency syndrome (Orphanet:252202), Hereditary breast cancer (Orphanet:227535), Hepatocellular carcinoma (Orphanet:88673), Diffuse large B-cell lymphoma (Orphanet:544), Lymphoma (Orphanet:223735), Burkitt lymphoma (Orphanet:543), Rhabdomyosarcoma (Orphanet:780), Familial isolated dilated cardiomyopathy (Orphanet:154), Pituitary carcinoma (Orphanet:300385)

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive 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:0001274	Agenesis of corpus callosum
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:0002282	Gray matter heterotopia
HP:0002354	Memory impairment
HP:0002376	Developmental regression
HP:0002516	Increased intracranial pressure

GWAS associations

0 associations (top):

MeSH disease descriptors (19)

Descriptor	Name	Tree numbers
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D002051	Burkitt Lymphoma	C01.925.256.466.313.165; C01.925.928.313.165; C04.557.386.480.150.165; C15.604.515.569.480.150.165; C20.683.515.761.480.150.165
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
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
D008223	Lymphoma	C04.557.386; C15.604.515.569; C20.683.515.761
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D055653	Muir-Torre Syndrome	C04.588.805.578.500; C04.700.250.500.500; C16.320.700.250.500.500; C17.800.794.712.500; C17.800.827.610; C17.800.882.712.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
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
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C562840	Breast Cancer, Familial (supp.)
C565824	Cardiomyopathy, Dilated, 1g (supp.)
C566044	Cardiomyopathy, Familial Hypertrophic, 9 (supp.)
C563971	Colorectal Cancer, Hereditary Nonpolyposis, Type 4 (supp.)
C563456	Colorectal Cancer, Hereditary Nonpolyposis, Type 5 (supp.)
C537261	Lynch syndrome I (site-specific colonic cancer) (supp.)
C536928	Turcot syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066497 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 oncogenic.

Variant	Therapy	Indication	Effect	Level	CIViC
PMS2 K706FS*19	Nivolumab	Glioblastoma	Sensitivity/Response	CIViC C	EID1214

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1062372	AIMP2, PMS2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects localization, affects cotreatment, increases expression	2
Methylnitrosourea	affects binding, increases reaction, increases response to substance	2
aristolochic acid I	increases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
methylselenic acid	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
O(6)-benzylguanine	affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
CPG-oligonucleotide	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
riccardin D	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	affects cotreatment, affects expression	1
Decitabine	increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Ethanol	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases expression, increases abundance	1
Carbon Tetrachloride	decreases expression	1
Estradiol	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652956	Binding	Binding affinity to human PMS2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

32 cell lines: 31 cancer cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0293	HEC-1-A	Cancer cell line	Female
CVCL_0294	HEC-1-B	Cancer cell line	Female
CVCL_1274	HEC-1	Cancer cell line	Female
CVCL_A5IQ	hTERT-1604-PMS134	Telomerase immortalized cell line	Male
CVCL_AR90	HEC-1-A-OZA1	Cancer cell line	Female
CVCL_AR91	HEC-1-A-OZA2	Cancer cell line	Female
CVCL_AR92	HEC-1-A-OZA3	Cancer cell line	Female
CVCL_AR93	HEC-1-A-OZA4	Cancer cell line	Female
CVCL_AR94	HEC-1-A-OZA5	Cancer cell line	Female
CVCL_AR95	HEC-1-A-OZA6	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
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NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	PHASE4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer