HM13

Summary

HM13 (histocompatibility minor 13, HGNC:16435) is a protein-coding gene on chromosome 20q11.21, encoding Signal peptide peptidase (Q8TCT9). Catalyzes intramembrane proteolysis of signal peptides that have been removed from precursors of secretory and membrane proteins, resulting in the release of the fragment from the ER membrane into the cytoplasm.

The protein encoded by this gene, which localizes to the endoplasmic reticulum, catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. This activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. The encoded protein is an integral membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases. Multiple transcript variants encoding several different isoforms have been found for this gene.

Source: NCBI Gene 81502 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• MANE Select transcript: NM_178581

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16435
Approved symbol	HM13
Name	histocompatibility minor 13
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	H13, dJ324O17.1, SPP, PSL3, IMP1, IMPAS, PSENL3, SPPL1
Ensembl gene	ENSG00000101294
Ensembl biotype	protein_coding
OMIM	607106
Entrez	81502

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 27 protein_coding, 14 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000340852, ENST00000344042, ENST00000398174, ENST00000460225, ENST00000460389, ENST00000464173, ENST00000466766, ENST00000468559, ENST00000469097, ENST00000469126, ENST00000472128, ENST00000474466, ENST00000483310, ENST00000487281, ENST00000492709, ENST00000493364, ENST00000494153, ENST00000496438, ENST00000498035, ENST00000619859, ENST00000649374, ENST00000649820, ENST00000650367, ENST00000674240, ENST00000894654, ENST00000894655, ENST00000894656, ENST00000894657, ENST00000894658, ENST00000894659, ENST00000894660, ENST00000894661, ENST00000894662, ENST00000894663, ENST00000915801, ENST00000915802, ENST00000915803, ENST00000915804, ENST00000942308, ENST00000942309, ENST00000942310, ENST00000942311, ENST00000942312, ENST00000942313, ENST00000942314

RefSeq mRNA: 4 — MANE Select: NM_178581 NM_030789, NM_178580, NM_178581, NM_178582

CCDS: CCDS13182, CCDS13183, CCDS42861

Canonical transcript exons

ENST00000398174 — 13 exons

Exon	Start	End
ENSE00001390560	31538179	31538261
ENSE00001531950	31568078	31568224
ENSE00001556098	31569120	31569543
ENSE00003505212	31566210	31566295
ENSE00003512404	31549207	31549332
ENSE00003579180	31559611	31559647
ENSE00003591033	31544947	31545035
ENSE00003610198	31554746	31554829
ENSE00003618603	31549029	31549114
ENSE00003647732	31527484	31527582
ENSE00003665454	31561634	31561736
ENSE00003689466	31550064	31550121
ENSE00003903968	31514442	31514734

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 218.5062 / max 1791.8367, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183961	217.9162	1827
183964	13.1235	1674
183966	0.2708	86
183965	0.2662	102
183967	0.0531	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.16	gold quality
stromal cell of endometrium	CL:0002255	99.06	gold quality
bone marrow cell	CL:0002092	98.92	gold quality
lower esophagus mucosa	UBERON:0035834	98.76	gold quality
pancreas	UBERON:0001264	98.52	gold quality
adenohypophysis	UBERON:0002196	98.51	gold quality
islet of Langerhans	UBERON:0000006	98.43	gold quality
esophagus mucosa	UBERON:0002469	98.29	gold quality
minor salivary gland	UBERON:0001830	98.13	gold quality
left adrenal gland	UBERON:0001234	98.11	gold quality
left adrenal gland cortex	UBERON:0035825	98.08	gold quality
endocervix	UBERON:0000458	98.01	gold quality
right adrenal gland	UBERON:0001233	97.99	gold quality
pituitary gland	UBERON:0000007	97.92	gold quality
right lobe of thyroid gland	UBERON:0001119	97.92	gold quality
ectocervix	UBERON:0012249	97.92	gold quality
saliva-secreting gland	UBERON:0001044	97.90	gold quality
monocyte	CL:0000576	97.88	gold quality
leukocyte	CL:0000738	97.87	gold quality
right adrenal gland cortex	UBERON:0035827	97.77	gold quality
body of stomach	UBERON:0001161	97.76	gold quality
upper lobe of left lung	UBERON:0008952	97.76	gold quality
right lobe of liver	UBERON:0001114	97.72	gold quality
left lobe of thyroid gland	UBERON:0001120	97.67	gold quality
granulocyte	CL:0000094	97.65	gold quality
mucosa of transverse colon	UBERON:0004991	97.63	gold quality
vermiform appendix	UBERON:0001154	97.57	gold quality
adrenal gland	UBERON:0002369	97.44	gold quality
metanephros cortex	UBERON:0010533	97.39	gold quality
mouth mucosa	UBERON:0003729	97.32	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	53.54
E-CURD-122	yes	50.45
E-HCAD-4	yes	43.14
E-HCAD-1	yes	32.47
E-MTAB-10553	yes	8.09
E-GEOD-93593	no	7.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting HM13, 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-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-6894-3P	96.73	65.64	798
HSA-MIR-1291	96.28	65.89	1224

Literature-anchored findings (GeneRIF, showing 19)

• identified human signal peptide peptidase as a polytopic membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases [SPP] (PMID:12077416)
• identification and molecular cloning; expression analysis of the hIMP1 gene (located on chromosome 20) was performed in human cell tissues and transfected cell cultures [IMP1] (PMID:12139484)
• widespread expression of SPP in many tissues (PMID:12972007)
• signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor (PMID:14704149)
• IMP1 is a bi-aspartic polytopic protease capable of cleaving transmembrane proteins such as presenilin 2. (PMID:14741365)
• The peptide structure corresponding to the C-terminal residues from H13 ribosomal protein was determined using magnetic resonance spectroscopy. (PMID:14988012)
• SPP, SPPL2a, -2b, -2c, and -3 probably cleave type II-oriented substrate peptides as shown by consensus analysis (PMID:15385547)
• Compares a variant from the mouse ortholog to the human gene. (PMID:16730383)
• data implicate SPP in the US2 pathway and indicate the possibility of a previously unknown function for this intramembrane-cleaving aspartic protease in dislocation from the endoplasmic reticulum (PMID:16738546)
• Upon isolation of membranes and solubilization with detergent, the biochemical characteristics of SPP are remarkably similar to gamma-secretase. (PMID:16834339)
• structure of human SPP [SPP] (PMID:21636854)
• This study identifies that SPP affects EGFRvIII secretion profiles and thus promotes tumor progression, providing further understanding of the formation of secreted vesicles and driving role of EGFRvIII in Glioblastoma. (PMID:28198167)
• Though far from complete, our knowledge on pathophysiological functions of SPP/SPPL proteases, in particular based on studies in mice, has been significantly increased over the last years. Based on this, inhibition of distinct SPP/SPPL proteases has been proposed as a novel therapeutic concept e.g. for the treatment of autoimmunity and viral or protozoal infections, as we will discuss in this review. (PMID:28624439)
• The domains involved in HO-1 translocation have been identified, and it was shown that SPP-mediated HO-1 cleavage is isoform-specific (HO-1 vs HO-2) and independent of heme oxygenase activity. (PMID:29155886)
• Preproinsulin signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during type 1 diabetes pathogenesis. (PMID:29343547)
• Study demonstrates that SPP is highly induced in lung and breast cancers and promotes tumor progression, at least in part, by facilitating the degradation of mTOR inhibitor FKBP8. (PMID:30348988)
• Histocompatibility Minor 13 (HM13), targeted by miR-760, exerts oncogenic role in breast cancer by suppressing autophagy and activating PI3K-AKT-mTOR pathway. (PMID:36153332)
• The role of SPP/SPPL intramembrane proteases in membrane protein homeostasis. (PMID:37625440)
• Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase. (PMID:38218226)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hm13	ENSDARG00000037846
mus_musculus	H13	ENSMUSG00000019188
rattus_norvegicus	Mcts2	ENSRNOG00000007738
drosophila_melanogaster	Spp	FBGN0031260
caenorhabditis_elegans		WBGENE00011481

Paralogs (4): SPPL2B (ENSG00000005206), SPPL2A (ENSG00000138600), SPPL3 (ENSG00000157837), SPPL2C (ENSG00000185294)

Protein

Protein identifiers

Signal peptide peptidase — Q8TCT9 (reviewed: Q8TCT9)

Alternative names: Intramembrane protease 1, Minor histocompatibility antigen H13, Presenilin-like protein 3, Signal peptide peptidase-like 1

All UniProt accessions (8): Q8TCT9, A0A075B6F6, A0A087WVH6, A0A0C4DGU3, A0A0S2Z5V7, A0A0S2Z6F0, A0A3B3IT72, A0A3B3IUB5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes intramembrane proteolysis of signal peptides that have been removed from precursors of secretory and membrane proteins, resulting in the release of the fragment from the ER membrane into the cytoplasm. Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides. May be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein. Involved in the intramembrane cleavage of the integral membrane protein PSEN1. Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner. May play a role in graft rejection.

Subunit / interactions. Monomer. Homodimer. Interacts with RNF139. Interacts with DERL1 and XBP1 isoform 1.

Subcellular location. Endoplasmic reticulum membrane. Membrane Cell membrane.

Tissue specificity. Widely expressed with highest levels in kidney, liver, placenta, lung, leukocytes and small intestine and reduced expression in heart and skeletal muscle. Expressed abundantly in the CNS with highest levels in thalamus and medulla.

Post-translational modifications. N-glycosylated.

Domain organisation. The first transmembrane domain may act as a type I signal anchor. The PAL motif is required for normal active site conformation.

Similarity. Belongs to the peptidase A22B family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TCT9-1	1	yes
Q8TCT9-2	2
Q8TCT9-4	4
Q8TCT9-5	5

RefSeq proteins (4): NP_110416, NP_848695, NP_848696, NP_848697 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006639	Preselin/SPP	Family
IPR007369	Peptidase_A22B_SPP	Family

Pfam: PF04258

UniProt features (43 total): topological domain 10, transmembrane region 9, mutagenesis site 6, sequence conflict 5, splice variant 3, region of interest 2, active site 2, glycosylation site 2, chain 1, short sequence motif 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCT9-F1	83.01	0.53

Functional residue map

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

Catalytic / active sites (2): 219; 265

Post-translational modifications (1): 367

Glycosylation sites (2): 10, 20

Mutagenesis-validated functional residues (6):

Position	Phenotype
10	abolishes n-glycosylation; when associated with q-20.
20	abolishes n-glycosylation; when associated with q-10.
219	abolishes proteolysis of psen1.
264	no effect on proteolysis of psen1.
265	no effect on inhibitor binding; abolishes signal peptide peptidase activity. abolishes proteolysis of psen1. abolishes p
317	abolishes proteolysis of psen1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9707587	Regulation of HMOX1 expression and activity

MSigDB gene sets: 202 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, RIZKI_TUMOR_INVASIVENESS_3D_DN, EFC_Q6, GOBP_PROTEIN_MATURATION, GOBP_MEMBRANE_PROTEIN_INTRACELLULAR_DOMAIN_PROTEOLYSIS, CYTAGCAAY_UNKNOWN, HTF_01, GOBP_MEMBRANE_PROTEIN_ECTODOMAIN_PROTEOLYSIS, RYTTCCTG_ETS2_B

GO Biological Process (6): in utero embryonic development (GO:0001701), obsolete signal peptide processing (GO:0006465), membrane protein proteolysis (GO:0033619), cellular response to oxidative stress (GO:0034599), membrane protein proteolysis involved in retrograde protein transport, ER to cytosol (GO:1904211), proteolysis (GO:0006508)

GO Molecular Function (6): peptidase activity (GO:0008233), ubiquitin protein ligase binding (GO:0031625), aspartic endopeptidase activity, intramembrane cleaving (GO:0042500), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), rough endoplasmic reticulum (GO:0005791), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), Derlin-1 retrotranslocation complex (GO:0036513), lumenal side of endoplasmic reticulum membrane (GO:0098553), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cytoprotection by HMOX1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endoplasmic reticulum membrane	3
cellular anatomical structure	2
chordate embryonic development	1
proteolysis	1
response to oxidative stress	1
cellular response to chemical stress	1
retrograde protein transport, ER to cytosol	1
membrane protein proteolysis	1
protein metabolic process	1
hydrolase activity	1
catalytic activity, acting on a protein	1
ubiquitin-like protein ligase binding	1
aspartic-type endopeptidase activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum	1
membrane	1
cell periphery	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
lumenal side of membrane	1
cytoplasmic side of membrane	1

Protein interactions and networks

STRING

1236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HM13	RNF139	Q8WU17	980
HM13	USH2A	O75445	889
HM13	MBTPS2	O43462	708
HM13	APH1A	Q96BI3	700
HM13	NCSTN	Q92542	687
HM13	PSENEN	Q9NZ42	653
HM13	RHBDL2	Q9NX52	617
HM13	MCTS2	A0A3B3IRV3	613
HM13	SPPL3	Q8TCT6	593
HM13	SREBF2	Q12772	570
HM13	PARL	Q9H300	568
HM13	PSEN1	P49768	556
HM13	A0A1W2PP11	A0A1W2PP11	533
HM13	UBAC2	Q8NBM4	532
HM13	APP	P05067	510

IntAct

94 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TMEM266	KDM1A	psi-mi:“MI:0914”(association)	0.670
HM13	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
HM13	DERL1	psi-mi:“MI:0915”(physical association)	0.520
DERL1	HM13	psi-mi:“MI:0915”(physical association)	0.520
HM13	RNF139	psi-mi:“MI:0915”(physical association)	0.520
XBP1	HM13	psi-mi:“MI:0915”(physical association)	0.520
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
pipB2	SCD	psi-mi:“MI:0914”(association)	0.460
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
P4HB	HM13	psi-mi:“MI:0915”(physical association)	0.400
HM13		psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (218): DERL1 (Affinity Capture-Western), RNF139 (Affinity Capture-Western), XBP1 (Affinity Capture-Western), HM13 (Affinity Capture-Western), LZTS2 (Two-hybrid), HM13 (Affinity Capture-MS), HM13 (Affinity Capture-MS), HM13 (Two-hybrid), ATP2B1 (Co-fractionation), ATP2B3 (Co-fractionation), ATP2B4 (Co-fractionation), HM13 (Affinity Capture-MS), HM13 (Affinity Capture-Western), HM13 (Proximity Label-MS), HM13 (Proximity Label-MS)

ESM2 similar proteins: A1CJW1, A1D7K7, A3LU53, A4R0J5, A5DGY3, A5JYQ9, A6R3V7, A6ZV87, A7F5K4, A7S6Y0, A7TSA7, B2WDD8, B3LIC1, B4UN04, B9TRX0, C6Y4C8, O13113, O15243, O22622, O24060, O65085, O94777, P0CS24, P0CS25, P41806, P52872, P53633, Q0CXF5, Q0UV26, Q18319, Q1HQF8, Q2HDV5, Q3SYT0, Q561T9, Q5B905, Q5PSV5, Q5RBB4, Q5ZJD9, Q6BXM0, Q6CDK3

Diamond homologs: A2A6C4, B9FJ61, O81062, P34248, P49049, Q0DWA9, Q0WMJ8, Q3TD49, Q4V3B8, Q53P98, Q5F383, Q5N808, Q5PQL3, Q5Z413, Q6ZGL9, Q7G7C7, Q8IUH8, Q8TCT7, Q8TCT8, Q8TCT9, Q8W469, Q9D8V0, Q9JJF9, Q9MA44, Q9UTA3, Q93Z32, Q8TCT6, Q9CUS9, Q6GQB9, P25152, O22925, P93026, Q9W1W9, Q2HXL6, Q9BZQ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
Regulation of RAS by GAPs	5	16.4×	5e-04
SLC-mediated transmembrane transport	6	6.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	16.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2378 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31514732:AAG:A	donor_loss	1.0000
20:31514734:GG:G	donor_loss	1.0000
20:31514735:GTAGG:G	donor_loss	1.0000
20:31514736:T:A	donor_loss	1.0000
20:31527482:A:AG	acceptor_gain	1.0000
20:31527482:A:G	acceptor_loss	1.0000
20:31527482:AGAAT:A	acceptor_gain	1.0000
20:31527483:G:GA	acceptor_gain	1.0000
20:31527483:GA:G	acceptor_gain	1.0000
20:31527483:GAA:G	acceptor_gain	1.0000
20:31527483:GAAT:G	acceptor_gain	1.0000
20:31527483:GAATG:G	acceptor_gain	1.0000
20:31527578:TCAAA:T	donor_gain	1.0000
20:31527579:CAAA:C	donor_gain	1.0000
20:31527580:AAA:A	donor_gain	1.0000
20:31527580:AAAG:A	donor_loss	1.0000
20:31527581:AA:A	donor_gain	1.0000
20:31527581:AAG:A	donor_loss	1.0000
20:31527582:AG:A	donor_loss	1.0000
20:31527583:G:GG	donor_gain	1.0000
20:31527583:GTA:G	donor_loss	1.0000
20:31527584:TAAGT:T	donor_loss	1.0000
20:31549110:GGAAG:G	donor_gain	1.0000
20:31549111:GAAG:G	donor_gain	1.0000
20:31549111:GAAGG:G	donor_gain	1.0000
20:31549112:A:T	donor_gain	1.0000
20:31549112:AAGGT:A	donor_loss	1.0000
20:31549113:AG:A	donor_gain	1.0000
20:31549114:GG:G	donor_gain	1.0000
20:31549115:G:A	donor_loss	1.0000

AlphaMissense

2786 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31514699:G:C	G50R	1.000
20:31514700:G:A	G50D	1.000
20:31527524:C:A	A75D	1.000
20:31527536:C:A	P79H	1.000
20:31527545:C:A	A82D	1.000
20:31527547:A:C	S83R	1.000
20:31527549:C:A	S83R	1.000
20:31527549:C:G	S83R	1.000
20:31527557:T:A	L86H	1.000
20:31538233:G:A	G113R	1.000
20:31538233:G:C	G113R	1.000
20:31549091:G:C	G173R	1.000
20:31549210:T:A	W182R	1.000
20:31549210:T:C	W182R	1.000
20:31549224:C:A	N186K	1.000
20:31549224:C:G	N186K	1.000
20:31549232:G:A	G189D	1.000
20:31549253:G:A	G196E	1.000
20:31549298:T:C	L211P	1.000
20:31549310:T:A	L215H	1.000
20:31549310:T:C	L215P	1.000
20:31549322:A:C	D219A	1.000
20:31549322:A:G	D219G	1.000
20:31549322:A:T	D219V	1.000
20:31549330:T:A	W222R	1.000
20:31549330:T:C	W222R	1.000
20:31550083:T:G	M229R	1.000
20:31550084:G:A	M229I	1.000
20:31550084:G:C	M229I	1.000
20:31550084:G:T	M229I	1.000

dbSNP variants (sampled 300 via entrez): RS1000010034 (20:31532194 A>C,G), RS1000037121 (20:31535099 G>A), RS1000052074 (20:31566528 C>A,G,T), RS1000143400 (20:31528974 C>A), RS1000275236 (20:31522430 C>T), RS1000324556 (20:31561903 G>C), RS1000324975 (20:31563980 G>A), RS1000344687 (20:31515573 C>T), RS1000377020 (20:31562288 G>T), RS1000433079 (20:31528679 G>A,C), RS1000453433 (20:31523664 C>T), RS1000506288 (20:31565497 A>C), RS1000570649 (20:31563707 A>T), RS1000582924 (20:31513562 T>C), RS1000652916 (20:31557346 C>T)

Disease associations

OMIM: gene MIM:607106 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009067_1	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-17
GCST010241_359	Apolipoprotein A1 levels	5.000000e-11
GCST010242_230	HDL cholesterol levels	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523407 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	Kd	9930	nM	CHEMBL3752910
5.00	ED50	9930	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148517: Binding affinity to human HM13 incubated for 45 mins by Kinobead based pull down assay	kd	9.9299	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
bisphenol A	affects expression, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
decabromobiphenyl ether	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
sulindac sulfide	affects binding, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
L 685458	affects binding, decreases reaction, decreases activity	1
1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression	1
2-(2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-(3-methyl-4-oxo-4,5-dihydro-3H-benzo(d)(1,2)diazepin-5-yl)propanamide	affects binding, decreases activity, decreases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341386	Binding	Binding affinity to HM13 in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2YS	Abcam HEK293T HM13 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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