HMMR

Summary

HMMR (hyaluronan mediated motility receptor, HGNC:5012) is a protein-coding gene on chromosome 5q34, encoding Hyaluronan mediated motility receptor (O75330). Receptor for hyaluronic acid (HA).

The protein encoded by this gene is involved in cell motility. It is expressed in breast tissue and together with other proteins, it forms a complex with BRCA1 and BRCA2, thus is potentially associated with higher risk of breast cancer. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Source: NCBI Gene 3161 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 132 total — 1 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_001142556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5012
Approved symbol	HMMR
Name	hyaluronan mediated motility receptor
Location	5q34
Locus type	gene with protein product
Status	Approved
Aliases	RHAMM, CD168
Ensembl gene	ENSG00000072571
Ensembl biotype	protein_coding
OMIM	600936
Entrez	3161

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000353866, ENST00000358715, ENST00000393915, ENST00000432118, ENST00000517936, ENST00000520345, ENST00000521108, ENST00000522094, ENST00000932207, ENST00000932208, ENST00000932209

RefSeq mRNA: 4 — MANE Select: NM_001142556 NM_001142556, NM_001142557, NM_012484, NM_012485

CCDS: CCDS4362, CCDS4363, CCDS47334, CCDS47335

Canonical transcript exons

ENST00000393915 — 18 exons

Exon	Start	End
ENSE00000484721	163473179	163473253
ENSE00000484727	163483020	163483172
ENSE00000768937	163473379	163473557
ENSE00000797323	163471185	163471271
ENSE00000797327	163474057	163474205
ENSE00000797329	163478684	163478800
ENSE00000797332	163483268	163483367
ENSE00000797333	163484069	163484245
ENSE00000797335	163490390	163490552
ENSE00001313019	163482642	163482788
ENSE00001330546	163475458	163475672
ENSE00001877646	163460632	163460738
ENSE00001883440	163491112	163491941
ENSE00003523944	163467701	163467748
ENSE00003565699	163463856	163463954
ENSE00003628610	163469641	163469829
ENSE00003684187	163464723	163464802
ENSE00003787411	163471363	163471463

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2277 / max 553.9949, expressed in 1428 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59972	20.2277	1428

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.70	gold quality
male germ cell	CL:0000015	95.19	gold quality
trabecular bone tissue	UBERON:0002483	90.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.73	gold quality
secondary oocyte	CL:0000655	87.24	gold quality
bone marrow	UBERON:0002371	86.96	gold quality
ventricular zone	UBERON:0003053	86.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.85	gold quality
embryo	UBERON:0000922	84.34	gold quality
bone marrow cell	CL:0002092	82.48	gold quality
testis	UBERON:0000473	82.09	gold quality
esophagus squamous epithelium	UBERON:0006920	82.02	gold quality
vermiform appendix	UBERON:0001154	81.55	gold quality
left testis	UBERON:0004533	81.34	gold quality
right testis	UBERON:0004534	81.31	gold quality
rectum	UBERON:0001052	80.62	gold quality
tibia	UBERON:0000979	80.14	gold quality
amniotic fluid	UBERON:0000173	79.81	gold quality
ganglionic eminence	UBERON:0004023	79.41	gold quality
adrenal tissue	UBERON:0018303	79.17	gold quality
squamous epithelium	UBERON:0006914	78.44	gold quality
mucosa of sigmoid colon	UBERON:0004993	77.19	gold quality
gingival epithelium	UBERON:0001949	77.16	gold quality
epithelium of esophagus	UBERON:0001976	77.16	gold quality
caecum	UBERON:0001153	77.05	gold quality
mucosa of transverse colon	UBERON:0004991	76.07	gold quality
colonic mucosa	UBERON:0000317	76.03	gold quality
duodenum	UBERON:0002114	76.01	gold quality
endometrium epithelium	UBERON:0004811	75.80	gold quality
oral cavity	UBERON:0000167	75.57	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	339.23
E-MTAB-10855	yes	286.58
E-GEOD-75140	yes	282.76
E-HCAD-13	yes	20.65
E-ANND-3	yes	5.93
E-MTAB-7249	no	432.47
E-MTAB-9689	no	338.48
E-MTAB-6911	no	217.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, E2F4, JUN, MTA1, TP53

miRNA regulators (miRDB)

51 targeting HMMR, 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-9-5P	100.00	72.28	2361
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-6768-3P	99.14	67.38	1319

Literature-anchored findings (GeneRIF, showing 40)

• Hyaluronate receptors mediate glioma cell migration and proliferation. The expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. (PMID:11716065)
• RHAMM is an immunogenic antigen expressed in leukemias and solid tumors and might be a potential target structure for cellular immunotherapies and antibody therapies. RHAMM is not expressed in normal tissues except for testis, placenta, thymus. (PMID:12225794)
• Increased RHAMM expression may enhance and improve the invasion and metastasis of endometrial carcinomas (PMID:12712331)
• Augmentation of RHAMM expression within human cancers, including myeloma, can directly affect centrosomal structure and spindle integrity and potentially modulate apoptotic and cell cycle progression pathways. (PMID:15705883)
• The overall results suggest that IHABP regulates the subcelluar localization of Bach1 in order to fine-tune transactivation of Bach1 target genes such as heme oxygenase-1. (PMID:15809329)
• RHAMM/CD168 R3-peptide (ILSLELMKL)-specific T-cell responses in chronic myeloid leukemia [CML] patients were demonstrated; vaccination strategies inducing such RHAMM-R3-directed effector T cells might enhance specific immune responses against CML cells. (PMID:17157168)
• an effect of CD44 on tumor cell motility may depend in part on its ability to partner with additional proteins, such as cell surface Rhamm. (PMID:17392272)
• These data suggest that high molecular form hyaluronan is broken down by reactive oxygen species to form low-molecular-weight fragments that signal via RHAMM and RON to stimulate beat frequency. (PMID:17395888)
• RHAMM is expressed in embryhonic stem cells (ESC) and has an important role in maintenance of ESC pluripotency and proliferation. (PMID:17872502)
• Overexpression of HMMR is associated with breast cancer (PMID:17922014)
• RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches (PMID:17978170)
• Androgen receptor regulates CD168 expression and signaling in prostate cancer (PMID:18174258)
• The unconventional export of proteins such as RHAMM is a novel process that modifies the roles of tumor suppressors and promoters, such as BRCA1 and CD44, and might provide new targets for therapeutic intervention. (PMID:18354082)
• Results suggested that in oral squamous cell carcinoma RHAMM expression may be correlated with tumor aggressiveness. (PMID:18425326)
• The combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in microsatellite instability-high colorectal cancer. (PMID:18559599)
• p53-dependent downregulation is consistent with an oncogenic function of RHAMM and the recently reported tumor-suppressive function of CD44 transcriptional repression by p53. (PMID:18971636)
• REVIEW. p53 represses RHAMM and CD44 expression (PMID:19001852)
• The reported association between common snps in HMMR and breast cancer risk is likely to be a false positive association. (PMID:19064580)
• Higher RHAMM expression in high-risk CLL patients, as well as in the advanced stages of the disease was associated with a significantly shorter median treatment-free survival. Stimulation with CD40L enhanced RHAMM expression in CLL. (PMID:19092852)
• A significant association was found between the mRNA expression levels of TPX and RHAMM in salivary gland carcinomas (PMID:19148505)
• We therefore investigated the expression and immunogenicity of two tumor-associated antigens (TAA) the receptor for hyaluronic acid mediated motility (RHAMM) and carboanhydrase IX (G250/CAIX) in HNSCC patients. (PMID:19212667)
• Overexpression of the receptor for hyaluronan-mediated motility is associated with oral squamous cell carcinomas. (PMID:19424574)
• maintained expression and even up-regulation of some (PNPT1, PMPCB, HMMR/RHAMM, BSG and ERCC1) tumor associated antigens in CD40-activated leukemic cells. (PMID:19580345)
• RHAMM (CD168) is overexpressed at the protein level and may constitute an immunogenic antigen in advanced prostate cancer disease. (PMID:19724689)
• coexpression of any of the CD44v with the receptor for hyaluronic acid-mediated motility (RHAMM, CD168) identifies a subgroup of DLBCL patients with a very poor prognosis, independent of the International Prognostic Index (PMID:19857547)
• RHAMM regulates the ciliary differentiation-promoting effect of retinoic acid on respiratory epithelial cells. (PMID:20619784)
• Nodular basal cell carcinoma is associated with increased levels of hyaluronic acid concomitant with upregulation of gene expression of HAS3, HYAL3 and RHAMM, when compared with normal adjacent skin. (PMID:20849445)
• study reports the new machinery by which RHAMM/ERK interaction induces the proliferative activity of cementifying fibroma cells via a specific signaling pathway through the CD44-EGFR axis (PMID:20956971)
• RHAMM not only represents a promising leukemia-associated antigens with specific T-cell responses in acute myeloid leukemia but, if assessed in situ on blasts, also a probable prognostic factor (PMID:21274712)
• tumor expression can be used as a prognostic marker of gastric cancer (PMID:21435222)
• RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways (PMID:21914806)
• Hyaluronan receptors in the human ocular surface: a descriptive and comparative study of RHAMM and CD44 in tissues, cell lines and freshly collected samples. (PMID:22095138)
• study depicts a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer (PMID:22110403)
• TCR-transgenic lymphocytes specific for HMMR/Rhamm limit tumor outgrowth in vivo. (PMID:22371883)
• RHAMM does not fulfill the criteria of an ideal target antigen for immunotherapy of acute myeloid leukemia. (PMID:22532518)
• Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels. (PMID:23166824)
• Data indicate that the sensitivity of cell-lines with amplification of AURKA depends upon the activity of the kinase, which correlates with the expression of the regulatory gene products TPX2 and HMMR/RHAMM. (PMID:23328114)
• Suggest that detection of upregulated RHAMM expression in an ossifying fibroma assists with differential diagnosis and has a key role in elucidation of its pathophysiology. (PMID:23382057)
• RHAMM plays a crucial role in mediating progression of muscle-invasive bladder cancer and recommends RHAMM for further evaluation as a prognostic marker or therapeutic target in bladder cancer therapy. (PMID:24069434)
• RHAMM transcription is regulated via YAP in a pathway involving mevalonate and Hippo that modulates breast cancer cell motility (PMID:24367099)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmmr	ENSDARG00000021794
mus_musculus	Hmmr	ENSMUSG00000020330
rattus_norvegicus	Hmmr	ENSRNOG00000059894

Protein

Protein identifiers

Hyaluronan mediated motility receptor — O75330 (reviewed: O75330)

Alternative names: Intracellular hyaluronic acid-binding protein, Receptor for hyaluronan-mediated motility

All UniProt accessions (3): O75330, E5RI30, E5RIH2

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for hyaluronic acid (HA). Involved in cell motility. When hyaluronan binds to HMMR, the phosphorylation of a number of proteins, including PTK2/FAK1 occurs. May also be involved in cellular transformation and metastasis formation, and in regulating extracellular-regulated kinase (ERK) activity. May act as a regulator of adipogenisis.

Subunit / interactions. Interacts with ANKRD26. Interacts with DYNLL1. Interacts with FAM83D/CHICA.

Subcellular location. Cell surface. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Expressed in testis. Expressed in the breast.

Isoforms (4)

UniProt ID	Names	Canonical?
O75330-1	1, A	yes
O75330-2	2, B
O75330-3	3
O75330-4	4

RefSeq proteins (4): NP_001136028, NP_001136029, NP_036616, NP_036617 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026203	IHABP	Family
IPR031794	HMMR_C	Domain

Pfam: PF15905, PF15908

UniProt features (31 total): sequence variant 8, sequence conflict 6, region of interest 5, glycosylation site 4, splice variant 3, compositionally biased region 2, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75330-F1	75.29	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 20, 703

Glycosylation sites (4): 133, 477, 567, 588

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2142845	Hyaluronan metabolism
R-HSA-2160916	Hyaluronan degradation
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 329 (showing top): MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, TGCGCANK_UNKNOWN, MORF_BUB1, GOBP_HYALURONAN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_16, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, KONG_E2F3_TARGETS

GO Biological Process (2): receptor-mediated endocytosis (GO:0006898), hyaluronan catabolic process (GO:0030214)

GO Molecular Function (4): hyaluronic acid binding (GO:0005540), cargo receptor activity (GO:0038024), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycosaminoglycan metabolism	1
Hyaluronan metabolism	1
G2/M Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	2
endocytosis	1
glycosaminoglycan catabolic process	1
hyaluronan metabolic process	1
carboxylic acid binding	1
molecular_function	1
vesicle-mediated transport	1
molecular adaptor activity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
cytoplasm	1
membrane	1
cell periphery	1
cytoskeleton	1

Protein interactions and networks

STRING

2930 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMMR	CD44	P16070	991
HMMR	BRCA1	P38398	912
HMMR	BRCA2	P51587	909
HMMR	TPX2	Q9ULW0	857
HMMR	AURKA	O14965	811
HMMR	DZIP1	Q86YF9	767
HMMR	HYAL2	Q12891	730
HMMR	STAB2	Q8WWQ8	711
HMMR	CCNB1	P14635	709
HMMR	LYVE1	Q9Y5Y7	703
HMMR	HAS2	Q92819	676
HMMR	CENPF	P49454	669
HMMR	SACK1D	Q9H4H8	644
HMMR	SKA3	Q8IX90	642
HMMR	ASPM	Q8IZT6	640

IntAct

109 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
TPX2	AURKA	psi-mi:“MI:0914”(association)	0.890
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
TBK1	TBKBP1	psi-mi:“MI:0914”(association)	0.860
CSNK1D	PER2	psi-mi:“MI:0914”(association)	0.810
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HMMR	MORN4	psi-mi:“MI:0915”(physical association)	0.670
MORN4	HMMR	psi-mi:“MI:0915”(physical association)	0.670
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
FAM83D	HMMR	psi-mi:“MI:0914”(association)	0.560
HMMR	FAM83D	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (172): MORN4 (Two-hybrid), HMMR (Affinity Capture-MS), HMMR (Affinity Capture-MS), CDH13 (Two-hybrid), GREB1 (Two-hybrid), IL24 (Two-hybrid), ITIH5 (Two-hybrid), NAT2 (Two-hybrid), THRSP (Two-hybrid), HMMR (Affinity Capture-MS), HMMR (Proximity Label-MS), HMMR (Proximity Label-MS), HMMR (Proximity Label-MS), HMMR (Proximity Label-MS), HMMR (Affinity Capture-MS)

ESM2 similar proteins: A0JMQ7, A0JMY4, A2AUM9, A2BDR7, A2BGP7, A6NI79, A6PWD2, A6QNP9, B1AJZ9, D3YV10, G9G127, O35550, O35551, O75330, O94986, P0CB05, Q05D60, Q0VFN8, Q0VFX2, Q15276, Q17QT2, Q3UPP8, Q498G2, Q4KLY0, Q4PJT6, Q4R703, Q4V7B0, Q5JU67, Q5NVN6, Q5U3A8, Q5U3Z6, Q5U4W1, Q5ZL12, Q66KE8, Q6DFC2, Q6DIS8, Q6IMY1, Q6NRC9, Q6P402, Q7M6Y5

Diamond homologs: O75330, P97779, Q00547, Q498L9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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
Aggrephagy	6	24.4×	2e-05
AURKA Activation by TPX2	9	22.5×	1e-07
COPI-independent Golgi-to-ER retrograde traffic	6	20.4×	4e-05
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	19.0×	5e-05
Loss of Nlp from mitotic centrosomes	7	18.2×	1e-05
Loss of proteins required for interphase microtubule organization from the centrosome	7	18.2×	1e-05
Post NMDA receptor activation events	5	16.7×	4e-04
Regulation of PLK1 Activity at G2/M Transition	8	16.6×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitotic cell cycle	6	9.2×	9e-03
protein phosphorylation	8	6.2×	9e-03
cell division	11	5.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	99
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2445322	NM_001142556.2(HMMR):c.2059G>T (p.Asp687Tyr)	Likely pathogenic

SpliceAI

2396 predictions. Top by Δscore:

Variant	Effect	Δscore
5:163463852:CTA:C	acceptor_loss	1.0000
5:163463853:TA:T	acceptor_loss	1.0000
5:163463854:A:AG	acceptor_gain	1.0000
5:163463854:A:T	acceptor_loss	1.0000
5:163463854:AG:A	acceptor_gain	1.0000
5:163463854:AGGTT:A	acceptor_gain	1.0000
5:163463855:G:A	acceptor_loss	1.0000
5:163463855:G:GT	acceptor_gain	1.0000
5:163463855:GG:G	acceptor_gain	1.0000
5:163463855:GGT:G	acceptor_gain	1.0000
5:163463855:GGTT:G	acceptor_gain	1.0000
5:163463855:GGTTG:G	acceptor_gain	1.0000
5:163463952:AAGG:A	donor_loss	1.0000
5:163463953:AG:A	donor_loss	1.0000
5:163463954:GG:G	donor_loss	1.0000
5:163463955:G:T	donor_loss	1.0000
5:163463956:T:G	donor_loss	1.0000
5:163464721:A:AG	acceptor_gain	1.0000
5:163464722:G:GG	acceptor_gain	1.0000
5:163464722:GA:G	acceptor_gain	1.0000
5:163464783:T:G	donor_gain	1.0000
5:163464798:CAAAG:C	donor_loss	1.0000
5:163464799:AAAGG:A	donor_loss	1.0000
5:163464800:AAG:A	donor_loss	1.0000
5:163464801:AGGT:A	donor_loss	1.0000
5:163464802:GG:G	donor_loss	1.0000
5:163464803:G:T	donor_loss	1.0000
5:163464804:T:A	donor_loss	1.0000
5:163469636:TCCA:T	acceptor_loss	1.0000
5:163469639:A:AG	acceptor_gain	1.0000

AlphaMissense

4826 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:163460723:T:C	F11L	0.992
5:163460725:C:A	F11L	0.992
5:163460725:C:G	F11L	0.992
5:163460699:T:C	F3L	0.986
5:163460701:T:A	F3L	0.986
5:163460701:T:G	F3L	0.986
5:163484194:A:C	Q636H	0.984
5:163484194:A:T	Q636H	0.984
5:163484199:T:C	I638T	0.981
5:163484238:T:C	L651P	0.981
5:163484076:T:C	L597P	0.980
5:163483362:T:C	F593L	0.978
5:163483364:T:A	F593L	0.978
5:163483364:T:G	F593L	0.978
5:163490403:T:C	L658P	0.977
5:163484208:T:A	V641D	0.975
5:163483342:T:C	L586P	0.974
5:163484199:T:G	I638S	0.974
5:163484185:T:A	N633K	0.972
5:163484185:T:G	N633K	0.972
5:163484139:T:C	L618P	0.971
5:163483320:T:A	W579R	0.969
5:163483320:T:C	W579R	0.969
5:163484217:T:C	L644S	0.969
5:163484179:T:A	H631Q	0.967
5:163484179:T:G	H631Q	0.967
5:163484197:A:C	K637N	0.964
5:163484197:A:T	K637N	0.964
5:163463939:T:C	F44L	0.962
5:163463941:T:A	F44L	0.962

dbSNP variants (sampled 300 via entrez): RS1000476811 (5:163468668 G>A), RS1000533993 (5:163469948 A>G), RS1000615303 (5:163476558 C>A), RS1000656177 (5:163473780 C>G), RS1000727247 (5:163475386 T>C), RS1000751940 (5:163483853 T>A,G), RS1000933849 (5:163487749 A>G), RS1000946454 (5:163474137 G>C,T), RS1000966498 (5:163489857 C>T), RS1001057358 (5:163481131 A>G), RS1001070216 (5:163476286 T>C), RS1001211374 (5:163468070 G>A), RS1001316121 (5:163468326 C>G,T), RS1001543703 (5:163481633 A>G), RS1001629526 (5:163469319 G>A,C)

Disease associations

OMIM: gene MIM:600936 | disease phenotypes: MIM:114480, MIM:167000

GenCC curated gene-disease

Mondo (2): hereditary breast carcinoma (MONDO:0016419), ovarian cancer (MONDO:0008170)

Orphanet (2): Hereditary breast cancer (Orphanet:227535), Rare ovarian cancer (Orphanet:213500)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003002	Breast carcinoma

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1024	Metabolite levels	2.000000e-06
GCST009391_1457	Metabolite levels	9.000000e-06
GCST009391_1864	Metabolite levels	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010361	lysophosphatidylcholine 18:2 measurement
EFO:0010405	triacylglycerol 48:2 measurement
EFO:0010410	triacylglycerol 50:3 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295676 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs299293	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs299313	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs299314	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs299293	HMMR	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs299314	HMMR	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs299313	HMMR	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil

ChEMBL bioactivities

12 potent at pChembl≥5 of 12 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.68	Kd	20.9	nM	CHEMBL4162476
7.62	Kd	24.2	nM	CHEMBL4175941
7.52	Kd	30.2	nM	CHEMBL4162476
7.50	Kd	31.9	nM	CHEMBL4168088
7.49	Kd	32.6	nM	CHEMBL4170615
7.36	Kd	43.3	nM	CHEMBL4175941
6.89	Kd	130	nM	CHEMBL4162693
6.70	Kd	201.8	nM	CHEMBL4170615
6.67	Kd	211.3	nM	CHEMBL4173160
6.58	Kd	265.1	nM	CHEMBL4162693
6.54	Kd	289.2	nM	CHEMBL4173160
6.48	Kd	331.1	nM	CHEMBL4168088

PubChem BioAssay actives

12 with measured affinity, of 85 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4S)-5-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-5-oxopentanoic acid	1363130: Inhibition of C-terminal His-tagged 7 kDa RHAMM (unknown origin) binding to HA after 240 secs by SPR method	kd	0.0209	uM
(4S)-5-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-[[2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoic acid	1363131: Inhibition of recombinant RHAMM (unknown origin) binding to HA after 240 secs by SPR method	kd	0.0242	uM
(4S)-5-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoic acid	1363130: Inhibition of C-terminal His-tagged 7 kDa RHAMM (unknown origin) binding to HA after 240 secs by SPR method	kd	0.0319	uM
(4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1363131: Inhibition of recombinant RHAMM (unknown origin) binding to HA after 240 secs by SPR method	kd	0.0326	uM
(4S)-4-[(2-aminoacetyl)amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1363131: Inhibition of recombinant RHAMM (unknown origin) binding to HA after 240 secs by SPR method	kd	0.1300	uM
(4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1363131: Inhibition of recombinant RHAMM (unknown origin) binding to HA after 240 secs by SPR method	kd	0.2113	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	6
Cisplatin	affects cotreatment, decreases expression, increases expression	5
Valproic Acid	affects expression, decreases expression	4
sodium arsenite	increases expression	3
Air Pollutants	increases abundance, affects cotreatment, decreases expression	3
Doxorubicin	decreases expression, affects response to substance	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Coumestrol	affects cotreatment, increases expression, affects reaction	2
Estradiol	decreases expression, increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, increases oxidation	2
Progesterone	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
kojic acid	decreases expression	1
trichostatin A	affects expression	1
dimethylselenide	decreases expression, increases oxidation	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
sulforaphane	decreases methylation, increases expression	1
cobaltous chloride	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4158245	Binding	Inhibition of C-terminal His-tagged 7 kDa RHAMM (unknown origin) binding to HA assessed as association constant at 1000 nM after 240 secs by SPR method	A truncated RHAMM protein for discovering novel therapeutic peptides. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1WS	Abcam A-549 HMMR KO	Cancer cell line	Male
CVCL_D2NI	Abcam THP-1 HMMR KO	Cancer cell line	Male
CVCL_SR55	HAP1 HMMR (-) 1	Cancer cell line	Male
CVCL_SR56	HAP1 HMMR (-) 2	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