HMSD

Summary

HMSD (histocompatibility minor serpin domain containing, HGNC:23037) is a protein-coding gene on chromosome 18q22.1, encoding Serpin-like protein HMSD (A8MTL9). Putative serine protease inhibitor.

This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen.

Source: NCBI Gene 284293 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001123366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23037
Approved symbol	HMSD
Name	histocompatibility minor serpin domain containing
Location	18q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ACC-6, ACC6
Ensembl gene	ENSG00000221887
Ensembl biotype	protein_coding
OMIM	612086
Entrez	284293

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000408945, ENST00000481726, ENST00000498680, ENST00000526932

RefSeq mRNA: 1 — MANE Select: NM_001123366 NM_001123366

CCDS: CCDS42441

Canonical transcript exons

ENST00000408945 — 4 exons

Exon	Start	End
ENSE00001574244	63960158	63961835
ENSE00001634694	63953354	63953527
ENSE00001921900	63949301	63949400
ENSE00003665913	63954408	63954557

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 84.86.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1683 / max 340.3712, expressed in 582 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170663	2.1777	443
170664	1.3536	246
170665	0.6370	143

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	84.86	gold quality
ventricular zone	UBERON:0003053	74.94	gold quality
substantia nigra	UBERON:0002038	74.38	gold quality
ganglionic eminence	UBERON:0004023	69.44	gold quality
Ammon’s horn	UBERON:0001954	68.31	gold quality
lymph node	UBERON:0000029	68.17	gold quality
hypothalamus	UBERON:0001898	68.04	gold quality
vermiform appendix	UBERON:0001154	65.68	gold quality
primary visual cortex	UBERON:0002436	65.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.04	gold quality
temporal lobe	UBERON:0001871	64.76	gold quality
cortical plate	UBERON:0005343	64.75	gold quality
amygdala	UBERON:0001876	64.66	gold quality
prefrontal cortex	UBERON:0000451	64.54	gold quality
cerebral cortex	UBERON:0000956	63.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.06	gold quality
corpus callosum	UBERON:0002336	62.56	gold quality
frontal cortex	UBERON:0001870	62.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.87	gold quality
putamen	UBERON:0001874	61.47	gold quality
anterior cingulate cortex	UBERON:0009835	61.25	gold quality
brain	UBERON:0000955	60.66	gold quality
right frontal lobe	UBERON:0002810	59.88	gold quality
upper lobe of left lung	UBERON:0008952	59.72	gold quality
tibial nerve	UBERON:0001323	58.45	gold quality
rectum	UBERON:0001052	58.40	gold quality
caudate nucleus	UBERON:0001873	58.38	gold quality
lung	UBERON:0002048	58.05	gold quality
nucleus accumbens	UBERON:0001882	57.17	gold quality
superior frontal gyrus	UBERON:0002661	56.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.57

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Serpin-like protein HMSD — A8MTL9 (reviewed: A8MTL9, P0C7T4)

Alternative names: Minor histocompatibility protein HMSD, Minor histocompatibility serpin domain-containing protein

All UniProt accessions (2): A8MTL9, P0C7T4

UniProt curated annotations — full annotation on UniProt →

Function. Putative serine protease inhibitor.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in dendritic cells and primary leukemia cells, especially those of myeloid lineage.

Similarity. Belongs to the serpin family.

Isoforms (2)

UniProt ID	Names	Canonical?
A8MTL9-1	1, HMSD	yes
P0C7T4-1	2, HMSD-v

RefSeq proteins (1): NP_001116838* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily

Pfam: PF00079

UniProt features (5 total): chain 2, signal peptide 1, glycosylation site 1, peptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MTL9-F1	79.98	0.24
AF-P0C7T4-F1	72.28	0.33

Functional residue map

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

Glycosylation sites (1): 50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CYTOKINE_PRODUCTION, chr18q22, GOBP_CYTOLYSIS, GOBP_POSITIVE_REGULATION_OF_TYPE_II_INTERFERON_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, ZNF597_TARGET_GENES, NABA_ECM_REGULATORS

GO Biological Process (3): activation of immune response (GO:0002253), cytolysis (GO:0019835), positive regulation of type II interferon production (GO:0032729)

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	1
positive regulation of immune response	1
cellular process	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMSD	ZNF419	Q96HQ0	571
HMSD	IL2RG	P31785	562
HMSD	CTSH	P09668	560
HMSD	HLA-B	P01889	549
HMSD	C11orf86	A6NJI1	479
HMSD	TOR3A	Q9H497	478
HMSD	CES1	P23141	454
HMSD	CENPM	Q9NSP4	418
HMSD	AKR1C8	Q5T2L2	417
HMSD	HMHB1	O97980	394
HMSD	BCL2A1	Q16548	371
HMSD	CFAP276	Q5T5A4	369
HMSD	PRSS36	Q5K4E3	362
HMSD	TMEM167B	Q9NRX6	360
HMSD	ASAH2B	P0C7U1	356

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2I7M9, A5PJK0, A8MTL9, A9RA96, B0CMB0, B1MTB7, B1MTC3, B2KI30, B3RFC3, B4USX2, E2RVI8, O04582, O73790, O73860, O75635, P01012, P01014, P05120, P09006, P12388, P19104, P29508, P29524, P29622, P32759, P36952, P48594, P48595, P70124, P70564, Q03044, Q52L45, Q5I2A0, Q5M8J5, Q5RCR2, Q6GLQ1, Q6V115, Q80X76, Q8CDC0, Q8K1K6

Diamond homologs: A2I7N0, A2I7N1, A5PJK0, A6QPQ2, A8MTL9, A9RA96, B0CMB0, B1MTC3, B2D1U1, B2KI30, B3RFC3, B4USX2, E1BF81, O00394, O02739, O08800, O54757, O54758, O54759, O54760, O54761, O54762, O54763, O73790, P01008, P01009, P01010, P01014, P05120, P05619, P07758, P07759, P08185, P09006, P12388, P12725, P17475, P22323, P22324, P22325

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1230 predictions. Top by Δscore:

Variant	Effect	Δscore
18:63954556:CA:C	donor_gain	1.0000
18:63954557:AG:A	donor_loss	1.0000
18:63954558:G:GG	donor_gain	1.0000
18:63954558:GT:G	donor_loss	1.0000
18:63954559:TAA:T	donor_loss	1.0000
18:63954560:AA:A	donor_loss	1.0000
18:63970168:G:GT	donor_gain	1.0000
18:63979939:G:GG	donor_gain	1.0000
18:63981712:T:TA	acceptor_gain	1.0000
18:63981716:TGCAG:T	acceptor_gain	1.0000
18:63981717:GCAGG:G	acceptor_gain	1.0000
18:63981718:CAGGA:C	acceptor_gain	1.0000
18:63981719:A:AG	acceptor_gain	1.0000
18:63981719:AG:A	acceptor_gain	1.0000
18:63981719:AGGAC:A	acceptor_gain	1.0000
18:63981720:G:A	acceptor_gain	1.0000
18:63981720:G:GA	acceptor_gain	1.0000
18:63981720:GGA:G	acceptor_gain	1.0000
18:63981720:GGAC:G	acceptor_gain	1.0000
18:63981720:GGACT:G	acceptor_gain	1.0000
18:63949398:GGG:G	donor_gain	0.9900
18:63949399:GG:G	donor_gain	0.9900
18:63949399:GGG:G	donor_gain	0.9900
18:63949399:GGGTA:G	donor_loss	0.9900
18:63949400:GG:G	donor_gain	0.9900
18:63949401:G:GG	donor_gain	0.9900
18:63949401:GT:G	donor_loss	0.9900
18:63954404:TCAGG:T	acceptor_gain	0.9900
18:63954405:CA:C	acceptor_loss	0.9900
18:63954405:CAGGC:C	acceptor_gain	0.9900

AlphaMissense

922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:63960161:T:C	F76L	0.954
18:63960163:T:A	F76L	0.954
18:63960163:T:G	F76L	0.954
18:63954528:T:C	F65L	0.939
18:63954530:T:A	F65L	0.939
18:63954530:T:G	F65L	0.939
18:63954459:T:C	F42L	0.928
18:63954461:T:A	F42L	0.928
18:63954461:T:G	F42L	0.928
18:63960212:T:C	F93L	0.924
18:63960214:T:A	F93L	0.924
18:63960214:T:G	F93L	0.924
18:63960182:T:C	F83L	0.890
18:63960184:C:A	F83L	0.890
18:63960184:C:G	F83L	0.890
18:63953495:G:C	A14P	0.867
18:63953459:A:C	S2R	0.856
18:63953461:C:A	S2R	0.856
18:63953461:C:G	S2R	0.856
18:63954549:T:C	F72L	0.847
18:63954551:C:A	F72L	0.847
18:63954551:C:G	F72L	0.847
18:63953520:T:C	M22T	0.841
18:63953492:G:T	G13W	0.839
18:63960191:G:C	A86P	0.807
18:63953492:G:A	G13R	0.787
18:63953492:G:C	G13R	0.787
18:63960162:T:C	F76S	0.786
18:63953477:G:C	A8P	0.784
18:63954417:T:C	F28L	0.768

dbSNP variants (sampled 300 via entrez): RS1000161655 (18:63961354 G>T), RS1000220067 (18:63960027 T>A), RS1000236114 (18:63966413 G>A), RS1000274470 (18:63948465 TATC>T), RS1000380111 (18:63954235 A>G), RS1000559043 (18:63948969 G>T), RS1000847532 (18:63960318 G>T), RS1001218803 (18:63959660 G>T), RS1001442839 (18:63961754 C>A,T), RS1001509039 (18:63947309 T>A,C), RS1001557025 (18:63952243 A>C,T), RS1001659408 (18:63964568 G>A), RS1001718027 (18:63958649 C>A,G), RS1001773360 (18:63958387 G>A,T), RS1002023694 (18:63966058 C>T)

Disease associations

OMIM: gene MIM:612086 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008916_98	Asthma	2.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
epigallocatechin gallate	decreases expression	1
pentanal	increases expression	1
ICG 001	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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