SAAL1

Summary

SAAL1 (serum amyloid A like 1, HGNC:25158) is a protein-coding gene on chromosome 11p15.1, encoding Protein SAAL1 (Q96ER3). Plays a role in promoting the proliferation of synovial fibroblasts in response to pro-inflammatory stimuli.

Acts upstream of or within positive regulation of synoviocyte proliferation. Located in nucleoplasm.

Source: NCBI Gene 113174 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• MANE Select transcript: NM_138421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25158
Approved symbol	SAAL1
Name	serum amyloid A like 1
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41463, SPACIA1
Ensembl gene	ENSG00000166788
Ensembl biotype	protein_coding
Entrez	113174

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 23 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000300013, ENST00000524803, ENST00000528002, ENST00000529318, ENST00000530180, ENST00000530237, ENST00000530436, ENST00000530736, ENST00000531216, ENST00000531581, ENST00000531751, ENST00000532403, ENST00000532452, ENST00000533851, ENST00000534721, ENST00000898174, ENST00000898175, ENST00000940259, ENST00000940260, ENST00000940261, ENST00000940262, ENST00000940263, ENST00000940264, ENST00000940265, ENST00000940266, ENST00000940267, ENST00000940268, ENST00000940269, ENST00000940270, ENST00000940271, ENST00000940272

RefSeq mRNA: 1 — MANE Select: NM_138421 NM_138421

CCDS: CCDS31439

Canonical transcript exons

ENST00000524803 — 12 exons

Exon	Start	End
ENSE00001106592	18089330	18089510
ENSE00001106596	18083535	18083731
ENSE00001106598	18090175	18090290
ENSE00001106600	18087143	18087225
ENSE00002156541	18080292	18080491
ENSE00002164197	18105907	18106082
ENSE00003477042	18090434	18090493
ENSE00003496112	18103233	18103346
ENSE00003558859	18092245	18092324
ENSE00003680373	18081411	18081503
ENSE00003682118	18086866	18087054
ENSE00003684745	18096771	18096854

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 92.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7669 / max 210.8419, expressed in 1798 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118911	15.7669	1798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.83	gold quality
ganglionic eminence	UBERON:0004023	90.74	gold quality
ventricular zone	UBERON:0003053	90.42	gold quality
ileal mucosa	UBERON:0000331	89.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.40	gold quality
tibialis anterior	UBERON:0001385	89.26	silver quality
cerebellar hemisphere	UBERON:0002245	89.11	gold quality
cerebellar cortex	UBERON:0002129	88.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.84	gold quality
calcaneal tendon	UBERON:0003701	88.68	gold quality
left ovary	UBERON:0002119	88.41	gold quality
cortical plate	UBERON:0005343	88.36	gold quality
tibial nerve	UBERON:0001323	88.28	gold quality
rectum	UBERON:0001052	87.97	gold quality
right ovary	UBERON:0002118	87.94	gold quality
mucosa of transverse colon	UBERON:0004991	87.89	gold quality
body of uterus	UBERON:0009853	87.56	gold quality
granulocyte	CL:0000094	86.97	gold quality
body of pancreas	UBERON:0001150	86.85	gold quality
endocervix	UBERON:0000458	86.80	gold quality
right uterine tube	UBERON:0001302	86.69	gold quality
cerebellum	UBERON:0002037	86.68	gold quality
smooth muscle tissue	UBERON:0001135	86.65	gold quality
bone marrow cell	CL:0002092	86.42	gold quality
ectocervix	UBERON:0012249	86.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.88	gold quality
left testis	UBERON:0004533	85.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.66	gold quality
spleen	UBERON:0002106	85.65	gold quality
ovary	UBERON:0000992	85.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.71

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Overexpression of SPACIA1/SAAL1, a newly identified gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans. (PMID:22127701)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	saal1	ENSDARG00000018681
mus_musculus	Saal1	ENSMUSG00000006763
drosophila_melanogaster	CG30467	FBGN0050467

Paralogs (3): SAA2 (ENSG00000134339), SAA4 (ENSG00000148965), SAA1 (ENSG00000173432)

Protein

Protein identifiers

Protein SAAL1 — Q96ER3 (reviewed: Q96ER3)

Alternative names: Synoviocyte proliferation-associated in collagen-induced arthritis protein 1

All UniProt accessions (9): Q96ER3, E9PL53, E9PMD2, E9PRZ1, G1UCX3, H0YCN7, H0YDM3, H0YEK5, J3KND1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in promoting the proliferation of synovial fibroblasts in response to pro-inflammatory stimuli.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis and ovary, and to a lesser extent in the lung, spleen and the heart (at protein level).

Similarity. Belongs to the SAAL1 family.

RefSeq proteins (1): NP_612430* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR052464	Synovial_Prolif_Regulator	Family

UniProt features (8 total): modified residue 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96ER3-F1	85.81	0.69

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): 6, 387

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, WEI_MYCN_TARGETS_WITH_E_BOX, FISCHER_DREAM_TARGETS, GOBP_EPITHELIAL_CELL_PROLIFERATION, RASHI_RESPONSE_TO_IONIZING_RADIATION_6, TGATTTRY_GFI1_01, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION, GSE14415_INDUCED_TREG_VS_FAILED_INDUCED_TREG_UP, ARID5B_TARGET_GENES, SFMBT1_TARGET_GENES, SKIL_TARGET_GENES, SNIP1_TARGET_GENES

GO Biological Process (1): positive regulation of synoviocyte proliferation (GO:1901647)

GO Molecular Function (0):

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), collagen trimer (GO:0005581)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synoviocyte proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of synoviocyte proliferation	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAAL1	PRAMEF20	Q5VT98	519
SAAL1	TMEM19	Q96HH6	506
SAAL1	ASGR2	P07307	494
SAAL1	SLA	Q13239	475
SAAL1	SERGEF	Q9UGK8	463
SAAL1	TANGO6	Q9C0B7	438
SAAL1	SAA4	P35542	436
SAAL1	ASGR1	P07306	420
SAAL1	OR51A2	Q8NGJ7	418
SAAL1	PLEKHM3	Q6ZWE6	407
SAAL1	APOC1	P02654	399
SAAL1	ISOC1	Q96CN7	398
SAAL1	VLDLR	P98155	396
SAAL1	APOC3	P02656	385
SAAL1	ZER1	Q7Z7L7	381

IntAct

172 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
CD68	TTI1	psi-mi:“MI:0914”(association)	0.640
	PMPCB	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
ZFPL1	PPP2R5E	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
CD68	LGALS1	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
CD4	CCDC85C	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
VASN	AP3B1	psi-mi:“MI:0914”(association)	0.530
FZD10	NRP1	psi-mi:“MI:0914”(association)	0.530
VSIG2	TTI1	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
CA14	EXOC5	psi-mi:“MI:0914”(association)	0.530

BioGRID (243): SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F9C6I2, A1L3F5, A2RT67, A4IIA7, A6NHR9, A7MBJ1, A8K855, D3ZXK7, F4JSE7, O08658, O14893, O75165, P0C8M4, P49021, Q0P410, Q3UD82, Q4R5A4, Q568D5, Q5F3F2, Q5R9R1, Q5RC14, Q5VVJ2, Q5XI20, Q5XPI3, Q5XPI4, Q5ZJK1, Q66J91, Q66KJ5, Q69Z66, Q6GPL9, Q7TMY8, Q7TNH6, Q7Z494, Q7Z6Z7, Q7ZX36, Q8BHR8, Q8CDG3, Q8CEC0, Q8CF97, Q8CGA4

Diamond homologs: Q6DCP5, Q6NVK9, Q803M5, Q96ER3, Q9D2C2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SAAL1	“up-regulates quantity by expression”	CDK6	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 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.

GO biological processes:

GO term	Partners	Fold	FDR
T cell costimulation	6	14.7×	3e-03

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	45
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2374 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18080490:ACCTG:A	acceptor_loss	1.0000
11:18080491:CCTGT:C	acceptor_loss	1.0000
11:18080492:CT:C	acceptor_loss	1.0000
11:18080493:T:G	acceptor_loss	1.0000
11:18081403:ATAC:A	donor_loss	1.0000
11:18081404:TACT:T	donor_loss	1.0000
11:18081405:ACT:A	donor_loss	1.0000
11:18081406:CTCA:C	donor_loss	1.0000
11:18081409:ACCAC:A	donor_loss	1.0000
11:18081410:C:CT	donor_loss	1.0000
11:18081410:CCA:C	donor_gain	1.0000
11:18081501:CTC:C	acceptor_gain	1.0000
11:18081503:CCTAA:C	acceptor_loss	1.0000
11:18081504:C:CA	acceptor_loss	1.0000
11:18081504:C:CC	acceptor_gain	1.0000
11:18081505:T:C	acceptor_loss	1.0000
11:18083580:AT:A	donor_gain	1.0000
11:18083581:T:TA	donor_gain	1.0000
11:18087055:C:CC	acceptor_gain	1.0000
11:18087056:T:C	acceptor_gain	1.0000
11:18087059:A:C	acceptor_gain	1.0000
11:18087221:CAGAA:C	acceptor_gain	1.0000
11:18087226:C:CC	acceptor_gain	1.0000
11:18089326:CTA:C	donor_loss	1.0000
11:18089327:TA:T	donor_loss	1.0000
11:18089328:A:AC	donor_gain	1.0000
11:18089329:C:CC	donor_gain	1.0000
11:18089329:CCGTA:C	donor_gain	1.0000
11:18089333:A:AC	donor_gain	1.0000
11:18089334:C:CC	donor_gain	1.0000

AlphaMissense

3156 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18103251:C:A	W77C	0.999
11:18103251:C:G	W77C	0.999
11:18103253:A:G	W77R	0.999
11:18103253:A:T	W77R	0.999
11:18090247:A:G	W173R	0.998
11:18090247:A:T	W173R	0.998
11:18096838:A:G	L89P	0.996
11:18103249:T:G	D78A	0.996
11:18090434:C:A	R158M	0.995
11:18090434:C:G	R158T	0.995
11:18092298:A:C	N120K	0.995
11:18092298:A:T	N120K	0.995
11:18090290:C:A	R158S	0.994
11:18090290:C:G	R158S	0.994
11:18092262:G:C	S132R	0.994
11:18092262:G:T	S132R	0.994
11:18092264:T:G	S132R	0.994
11:18092312:C:G	G116R	0.994
11:18092312:C:T	G116R	0.994
11:18103249:T:A	D78V	0.994
11:18103250:C:G	D78H	0.994
11:18092302:C:T	G119D	0.993
11:18092311:C:T	G116E	0.992
11:18096828:A:C	F92L	0.992
11:18096828:A:T	F92L	0.992
11:18096830:A:G	F92L	0.992
11:18096847:G:T	A86D	0.992
11:18103244:A:G	S80P	0.992
11:18103248:A:C	D78E	0.991
11:18103248:A:T	D78E	0.991

dbSNP variants (sampled 300 via entrez): RS1000105033 (11:18105527 T>C), RS1000141027 (11:18105206 G>A,C,T), RS1000169912 (11:18086797 G>T), RS1000412021 (11:18098975 T>C), RS1000508834 (11:18095155 T>A,C), RS1000525912 (11:18082520 A>T), RS1000579062 (11:18082215 A>G), RS1000689889 (11:18099700 G>C), RS1000945879 (11:18094409 A>G), RS1001112955 (11:18106407 G>A), RS1001126247 (11:18097850 A>C), RS1001135234 (11:18086726 AAAAT>A), RS1001241168 (11:18088780 G>A,C), RS1001310752 (11:18093302 T>C), RS1001386054 (11:18100799 T>C)

Disease associations

OMIM: gene `` | 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: yes

ChEMBL targets (1): CHEMBL6067380 (SINGLE PROTEIN)

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
bisphenol A	decreases expression, decreases methylation, increases expression	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Arsenic	affects cotreatment, increases abundance, increases expression, affects methylation	2
Valproic Acid	affects expression, increases expression	2
dicrotophos	decreases expression	1
K 7174	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Lead	affects expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652377	Binding	Binding affinity to human SAAL1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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