SMLR1

Summary

SMLR1 (small leucine rich protein 1, HGNC:44670) is a protein-coding gene on chromosome 6q23.1, encoding Small leucine-rich protein 1 (H3BR10).

Predicted to be located in membrane.

Source: NCBI Gene 100507203 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001195597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44670
Approved symbol	SMLR1
Name	small leucine rich protein 1
Location	6q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000256162
Ensembl biotype	protein_coding
OMIM	621362
Entrez	100507203

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000541421

RefSeq mRNA: 1 — MANE Select: NM_001195597 NM_001195597

CCDS: CCDS59036

Canonical transcript exons

ENST00000541421 — 2 exons

Exon	Start	End
ENSE00002281532	130827406	130827651
ENSE00002320355	130834870	130837135

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 94.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3075 / max 68.3336, expressed in 59 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69772	0.3075	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	94.08	gold quality
liver	UBERON:0002107	90.94	gold quality
right lobe of liver	UBERON:0001114	90.42	gold quality
ileal mucosa	UBERON:0000331	85.15	gold quality
duodenum	UBERON:0002114	83.78	gold quality
kidney epithelium	UBERON:0004819	75.02	silver quality
jejunum	UBERON:0002115	70.11	gold quality
pancreatic ductal cell	CL:0002079	65.72	silver quality
small intestine	UBERON:0002108	63.83	gold quality
tibialis anterior	UBERON:0001385	62.98	silver quality
adult mammalian kidney	UBERON:0000082	61.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	60.95	gold quality
kidney	UBERON:0002113	58.34	gold quality
buccal mucosa cell	CL:0002336	57.47	gold quality
deltoid	UBERON:0001476	56.59	silver quality
oviduct epithelium	UBERON:0004804	55.75	silver quality
epithelial cell of pancreas	CL:0000083	55.34	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
amniotic fluid	UBERON:0000173	53.60	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
oocyte	CL:0000023	52.90	gold quality
sural nerve	UBERON:0015488	52.37	gold quality
lower lobe of lung	UBERON:0008949	52.24	silver quality
cortex of kidney	UBERON:0001225	52.15	gold quality
cerebellar vermis	UBERON:0004720	51.65	gold quality
quadriceps femoris	UBERON:0001377	51.15	gold quality
right adrenal gland cortex	UBERON:0035827	50.82	gold quality
myocardium	UBERON:0002349	50.25	gold quality
adrenal tissue	UBERON:0018303	49.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting SMLR1, 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-4692	100.00	67.32	2066
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-519A-3P	99.67	71.67	1868

Literature-anchored findings (GeneRIF, showing 1)

• Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion. (PMID:36053190)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smlr1	ENSMUSG00000096546
rattus_norvegicus	Smlr1	ENSRNOG00000077441

Protein

Protein identifiers

Small leucine-rich protein 1 — H3BR10 (reviewed: H3BR10)

All UniProt accessions (1): H3BR10

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001182526* (*=MANE)

Domains & families (InterPro)

UniProt features (4 total): transmembrane region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-H3BR10-F1	65.89	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): VECCHI_GASTRIC_CANCER_EARLY_DN, chr6q23, OHGUCHI_LIVER_HNF4A_TARGETS_DN, ZSCAN2_TARGET_GENES, MIR4307, MIR5003_3P, MIR4692, MIR4514, MIR758_3P, MIR6073, MIR4714_5P, MIR1287_5P, MIR218_2_3P, MIR4489, MIR9900

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMLR1	CXorf58	Q96LI9	770
SMLR1	EFCAB3	Q8N7B9	599
SMLR1	CENPBD1P	B2RD01	584
SMLR1	C7orf25	Q9BPX7	580
SMLR1	TMEM244	Q5VVB8	574
SMLR1	RSRP1	Q9BUV0	507
SMLR1	HUS1B	Q8NHY5	506
SMLR1	SMIM3	Q9BZL3	477
SMLR1	TSEN54	Q7Z6J9	422
SMLR1	UFSP2	Q9NUQ7	418
SMLR1	BSCL2	Q96G97	397
SMLR1	ZNF335	Q9H4Z2	394
SMLR1	SLC22A16	Q86VW1	369
SMLR1	TAF4	O00268	318
SMLR1	GPR68	Q15743	290

IntAct

4 interactions, top by confidence:

A	B	Type	Score
BSCL2	SMLR1	psi-mi:“MI:0915”(physical association)	0.560
SMLR1	BSCL2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (2): SMLR1 (Two-hybrid), SMLR1 (Positive Genetic)

ESM2 similar proteins: A0A1B0GQX3, A0A1B0GRQ0, A0A1B0GV90, A0A1B0GVT2, A0A590UK83, A4QNL6, A5D7B5, A7RYM7, B0YA61, B3DHH5, C0HJJ0, D3YUK8, G1TZA0, H3BR10, O13001, O22752, O43073, O75324, P0C2S0, P0DKX4, P47111, P57054, P58550, P59648, P59649, P61807, P61808, Q12016, Q17Q87, Q3E8L0, Q3E912, Q3T0S0, Q3URE8, Q4V921, Q4WCL2, Q5RBD8, Q5XV67, Q80ZU4, Q8BT42, Q8LBX7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

161 predictions. Top by Δscore:

Variant	Effect	Δscore
6:130827648:GAGG:G	donor_gain	1.0000
6:130827650:GG:G	donor_gain	1.0000
6:130827651:GG:G	donor_gain	1.0000
6:130834868:A:AG	acceptor_gain	1.0000
6:130834869:G:GG	acceptor_gain	1.0000
6:130827647:TGAGG:T	donor_gain	0.9900
6:130827648:GAGGG:G	donor_gain	0.9900
6:130827649:AGGG:A	donor_loss	0.9900
6:130827650:GGGT:G	donor_loss	0.9900
6:130827652:G:C	donor_loss	0.9900
6:130827652:G:GG	donor_gain	0.9900
6:130827653:T:G	donor_loss	0.9900
6:130834869:GTT:G	acceptor_gain	0.9900
6:130834869:GTTA:G	acceptor_gain	0.9900
6:130827649:AGG:A	donor_gain	0.9800
6:130827650:GGG:G	donor_gain	0.9800
6:130827465:A:T	donor_gain	0.9400
6:130834864:TTTCA:T	acceptor_loss	0.9300
6:130834865:TTCA:T	acceptor_loss	0.9300
6:130834866:TCA:T	acceptor_loss	0.9300
6:130834867:CAGTT:C	acceptor_loss	0.9300
6:130834868:A:G	acceptor_loss	0.9300
6:130834869:GT:G	acceptor_gain	0.9200
6:130834783:A:G	donor_gain	0.9100
6:130827635:G:GT	donor_gain	0.8900
6:130834869:GTTAA:G	acceptor_gain	0.8800
6:130827477:GTCC:G	donor_gain	0.8400
6:130827478:TCCT:T	donor_gain	0.8400
6:130827656:GT:G	donor_gain	0.8400
6:130827654:A:AG	donor_loss	0.8200

AlphaMissense

693 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:130827595:C:G	P61R	0.961
6:130827588:T:C	F59L	0.947
6:130827590:C:A	F59L	0.947
6:130827590:C:G	F59L	0.947
6:130827595:C:A	P61H	0.947
6:130827583:G:A	G57E	0.944
6:130827619:T:A	L69H	0.932
6:130827592:T:G	L60R	0.927
6:130827610:T:G	L66R	0.922
6:130827643:T:C	L77P	0.921
6:130827582:G:A	G57R	0.910
6:130827582:G:C	G57R	0.910
6:130827619:T:G	L69R	0.904
6:130827592:T:A	L60H	0.902
6:130827607:T:G	L65R	0.902
6:130827610:T:A	L66Q	0.900
6:130827635:G:C	R74S	0.895
6:130827635:G:T	R74S	0.895
6:130827631:T:C	F73S	0.890
6:130827586:T:A	V58D	0.875
6:130827607:T:A	L65Q	0.874
6:130827625:C:A	A71D	0.872
6:130827610:T:C	L66P	0.871
6:130827574:T:A	L54Q	0.868
6:130827613:T:G	L67R	0.868
6:130827546:T:C	F45L	0.866
6:130827548:C:A	F45L	0.866
6:130827548:C:G	F45L	0.866
6:130827634:G:T	R74M	0.866
6:130827574:T:G	L54R	0.864

dbSNP variants (sampled 300 via entrez): RS1000003991 (6:130836697 C>T), RS1000267077 (6:130836418 C>G), RS1001019098 (6:130833824 T>C), RS1001251294 (6:130829699 A>T), RS1001440586 (6:130832374 G>A), RS1001487008 (6:130836019 TAC>T), RS1001548059 (6:130831813 T>A), RS1001745964 (6:130832584 A>C), RS1001831557 (6:130837216 G>A,C), RS1001850987 (6:130835740 A>G), RS1001967608 (6:130836937 C>A,T), RS1002456916 (6:130837031 T>C), RS1002896759 (6:130837288 C>T), RS1002991858 (6:130828516 T>G), RS1003015976 (6:130831339 T>A)

Disease associations

OMIM: gene MIM:621362 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010152_6	Neuroblastoma or malignant cutaneous melanoma	9.000000e-06
GCST90020028_189	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Aldehydes	decreases expression	1
Formaldehyde	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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