SMR3A

Summary

SMR3A (submaxillary gland androgen regulated protein 3A, HGNC:19216) is a protein-coding gene on chromosome 4q13.3, encoding Submaxillary gland androgen-regulated protein 3A (Q99954). May play a role in protection or detoxification.

Predicted to enable endopeptidase inhibitor activity. Predicted to be involved in regulation of sensory perception of pain. Predicted to be located in extracellular region.

Source: NCBI Gene 26952 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_012390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19216
Approved symbol	SMR3A
Name	submaxillary gland androgen regulated protein 3A
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	PBI, PRL5
Ensembl gene	ENSG00000109208
Ensembl biotype	protein_coding
OMIM	618340
Entrez	26952

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000226460

RefSeq mRNA: 1 — MANE Select: NM_012390 NM_012390

CCDS: CCDS34000

Canonical transcript exons

ENST00000226460 — 3 exons

Exon	Start	End
ENSE00000720235	70366644	70367158
ENSE00002447817	70362102	70362169
ENSE00002483352	70360760	70360842

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 99.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3957 / max 1147.9082, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47916	1.3957	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.74	gold quality
palpebral conjunctiva	UBERON:0001812	83.51	gold quality
tendon of biceps brachii	UBERON:0008188	82.30	silver quality
nasal cavity mucosa	UBERON:0001826	71.94	gold quality
buccal mucosa cell	CL:0002336	71.15	silver quality
trachea	UBERON:0003126	66.41	gold quality
diaphragm	UBERON:0001103	62.99	gold quality
vena cava	UBERON:0004087	58.42	gold quality
lower lobe of lung	UBERON:0008949	54.44	silver quality
oocyte	CL:0000023	54.38	gold quality
saliva-secreting gland	UBERON:0001044	54.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.54	gold quality
right lobe of thyroid gland	UBERON:0001119	52.01	gold quality
thyroid gland	UBERON:0002046	50.65	gold quality
left lobe of thyroid gland	UBERON:0001120	50.54	gold quality
tongue	UBERON:0001723	50.28	silver quality
caput epididymis	UBERON:0004358	49.96	gold quality
superior surface of tongue	UBERON:0007371	49.77	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.54	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
epithelial cell of pancreas	CL:0000083	49.19	gold quality
quadriceps femoris	UBERON:0001377	49.19	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
deltoid	UBERON:0001476	49.07	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
tonsil	UBERON:0002372	48.81	gold quality
vastus lateralis	UBERON:0001379	48.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting SMR3A, 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-6748-5P	100.00	65.81	1057
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-1229-5P	94.57	65.78	487

Literature-anchored findings (GeneRIF, showing 4)

• Results suggest that hSMR3A can act as a marker for erectile dysfunction associated with both diabetic and non-diabetic etiologies. (PMID:17512016)
• All members of the human opiorphin family of genes can potentially modulate erectile physiology. Both hSMR3 and ProL1 are down-regulated in the corpora of men with ED, and therefore both genes can potentially act as markers of ED. (PMID:18410445)
• High SMR3A expression is associated with aberrant differentiation into mucosal- or glandular-like cells in Adenoid Cystic Carcinoma of the Head and Neck. (PMID:26851015)
• Results show prominent SMR3A expression in head and neck squamous cell carcinoma, which was accompanied by an up-regulation of ESR2. These data suggest a critical role of ESR2 in radio-resistance and that SMR3A might serve as a surrogate marker for active ESR2 signaling. (PMID:28166815)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Submaxillary gland androgen-regulated protein 3A — Q99954 (reviewed: Q99954)

Alternative names: Proline-rich protein 5, Proline-rich protein PBI

All UniProt accessions (1): Q99954

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in protection or detoxification.

Subcellular location. Secreted.

Similarity. Belongs to the PROL1/PROL3 family.

RefSeq proteins (1): NP_036522* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026288	SMR-like	Family

Pfam: PF15621

UniProt features (9 total): compositionally biased region 3, sequence variant 3, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99954-F1	63.99	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_BCELL_DN, chr4q13, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_REGULATION_OF_SENSORY_PERCEPTION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, PRC2_EED_DN.V1_UP, PDGF_UP.V1_DN

GO Biological Process (1): regulation of sensory perception of pain (GO:0051930)

GO Molecular Function (2): endopeptidase inhibitor activity (GO:0004866), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of pain	1
regulation of sensory perception	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMR3A	PTP4A2	Q12974	541
SMR3A	CABS1	Q96KC9	470
SMR3A	PDPN	Q86YL7	410
SMR3A	FOXO3	O43524	377
SMR3A	PRL	P01236	377
SMR3A	MAGEB16	A2A368	367
SMR3A	PRB2	P02811	357
SMR3A	PRLR	P16471	311
SMR3A	PNLIPRP3	Q17RR3	311
SMR3A	CST5	P28325	308
SMR3A	PUDP	Q08623	289
SMR3A	GALNTL5	Q7Z4T8	285
SMR3A	CRCT1	Q9UGL9	275
SMR3A	SERPINB12	Q96P63	264
SMR3A	KCNMA1	Q12791	258
SMR3A	CHID1	Q9BWS9	258

IntAct

15 interactions, top by confidence:

A	B	Type	Score
WWP2	SMR3A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	SMR3A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-3	SMR3A	psi-mi:“MI:0915”(physical association)	0.560
SMR3A	WWOX	psi-mi:“MI:0915”(physical association)	0.560
SMR3A	VMAC	psi-mi:“MI:0914”(association)	0.530
SMR3A	WWP2	psi-mi:“MI:0915”(physical association)	0.000
SMR3A	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.000
SMR3A	KRTAP19-3	psi-mi:“MI:0915”(physical association)	0.000
SMR3A	WWOX	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): VMAC (Affinity Capture-MS), VMAC (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), KRTAP8-1 (Two-hybrid), WWOX (Two-hybrid), WWP2 (Two-hybrid), KRTAP19-3 (Two-hybrid), VMAC (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), SMR3A (Affinity Capture-MS)

ESM2 similar proteins: A5PJN8, A7RJ12, A7RNZ0, C0P381, C4NZN9, D3Z9M3, P02810, P02814, P02817, P02894, P04474, P06680, P06914, P06915, P08462, P08568, P08798, P10163, P10164, P10165, P11994, P13468, P18169, P18170, P18171, P18897, P21574, P21748, P23093, P23507, P51524, P75330, Q01493, Q05904, Q15428, Q16378, Q23933, Q26264, Q27270, Q28462

Diamond homologs: P02814, P13432, Q99935, Q99954, O09133, O35979, O35985, Q61900

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

193 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70362100:A:AG	acceptor_gain	1.0000
4:70362101:G:GG	acceptor_gain	1.0000
4:70362101:GA:G	acceptor_gain	1.0000
4:70362101:GAGGC:G	acceptor_gain	1.0000
4:70362166:CACAG:C	donor_loss	1.0000
4:70362168:CA:C	donor_gain	1.0000
4:70362168:CAG:C	donor_loss	1.0000
4:70362169:AG:A	donor_loss	1.0000
4:70362170:G:GG	donor_gain	1.0000
4:70362171:TA:T	donor_loss	1.0000
4:70362172:AA:A	donor_loss	1.0000
4:70362094:A:AG	acceptor_gain	0.9900
4:70362095:C:G	acceptor_gain	0.9900
4:70362096:TTTCA:T	acceptor_loss	0.9900
4:70362097:TTCA:T	acceptor_loss	0.9900
4:70362100:A:AC	acceptor_loss	0.9900
4:70362100:AGAG:A	acceptor_gain	0.9900
4:70362101:GAGG:G	acceptor_gain	0.9900
4:70362165:TCACA:T	donor_gain	0.9900
4:70362166:CACA:C	donor_gain	0.9900
4:70362167:ACA:A	donor_gain	0.9900
4:70362173:AGTAT:A	donor_loss	0.9900
4:70360841:AGG:A	donor_loss	0.9800
4:70360842:GGTA:G	donor_loss	0.9800
4:70360843:G:GA	donor_loss	0.9800
4:70360844:T:A	donor_loss	0.9700
4:70360843:G:GG	donor_gain	0.9600
4:70362099:CAG:C	acceptor_gain	0.9600
4:70362100:AGA:A	acceptor_gain	0.9600
4:70362101:G:C	acceptor_gain	0.9600

AlphaMissense

825 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:70362164:T:C	F17L	0.941
4:70362166:C:A	F17L	0.941
4:70362166:C:G	F17L	0.941
4:70362140:G:C	G9R	0.924
4:70362161:T:C	C16R	0.892
4:70362141:G:A	G9D	0.881
4:70362146:T:A	W11R	0.862
4:70362146:T:C	W11R	0.862
4:70362153:T:A	L13H	0.850
4:70362165:T:C	F17S	0.842
4:70366653:A:C	S22R	0.833
4:70366655:T:A	S22R	0.833
4:70366655:T:G	S22R	0.833
4:70366722:T:C	F45L	0.832
4:70366724:T:A	F45L	0.832
4:70366724:T:G	F45L	0.832
4:70362150:C:A	A12D	0.792
4:70366734:T:C	F49L	0.791
4:70366736:T:A	F49L	0.791
4:70366736:T:G	F49L	0.791
4:70362144:T:A	L10H	0.784
4:70362149:G:C	A12P	0.749
4:70362163:T:G	C16W	0.745
4:70362165:T:G	F17C	0.742
4:70362144:T:C	L10P	0.732
4:70362153:T:C	L13P	0.729
4:70362164:T:A	F17I	0.720
4:70362153:T:G	L13R	0.717
4:70366651:A:T	E21V	0.715
4:70362120:A:T	K2I	0.696

dbSNP variants (sampled 300 via entrez): RS1000165653 (4:70359989 C>T), RS1000259349 (4:70359132 T>A,C), RS1000440092 (4:70365749 C>T), RS1000499343 (4:70358891 A>T), RS1000744034 (4:70364637 T>A), RS10007796 (4:70360488 C>G,T), RS1001609609 (4:70359203 G>C), RS1001792278 (4:70365463 C>T), RS1001956679 (4:70367449 C>A,T), RS10024123 (4:70366713 T>C), RS1002668087 (4:70364215 G>A), RS1003023997 (4:70363888 A>G), RS10031674 (4:70366507 G>A,T), RS10031844 (4:70366671 G>A), RS1003617594 (4:70362331 T>C)

Disease associations

OMIM: gene MIM:618340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	increases reaction, affects binding	1
Arsenic Trioxide	affects binding, decreases reaction	1
Cadmium	decreases expression	1
Folic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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