ADAMTSL5

Summary

ADAMTSL5 (ADAMTS like 5, HGNC:27912) is a protein-coding gene on chromosome 19p13.3, encoding ADAMTS-like protein 5 (Q6ZMM2). May play a role in modulation of fibrillin microfibrils in the extracellular matrix (ECM).

Enables heparin binding activity and microfibril binding activity. Predicted to be involved in extracellular matrix organization. Located in extracellular region and microfibril.

Source: NCBI Gene 339366 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_213604

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27912
Approved symbol	ADAMTSL5
Name	ADAMTS like 5
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185761
Ensembl biotype	protein_coding
Entrez	339366

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000330475, ENST00000395467, ENST00000585700, ENST00000585804, ENST00000586272, ENST00000589839, ENST00000590090, ENST00000590440, ENST00000590562, ENST00000590682, ENST00000591077, ENST00000964292

RefSeq mRNA: 2 — MANE Select: NM_213604 NM_001367197, NM_213604

CCDS: CCDS12071

Canonical transcript exons

ENST00000330475 — 12 exons

Exon	Start	End
ENSE00002205003	1510845	1511160
ENSE00002773014	1512963	1513019
ENSE00003609233	1506590	1506661
ENSE00003610348	1510368	1510428
ENSE00003661552	1508443	1508570
ENSE00003691385	1507242	1507405
ENSE00003788252	1510150	1510258
ENSE00003988632	1507998	1508109
ENSE00003988634	1510639	1510730
ENSE00003988639	1507557	1507643
ENSE00003988647	1506739	1506928
ENSE00003988649	1505022	1506316

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 92.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.3263 / max 81.2498, expressed in 961 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178031	2.0418	902
178033	0.1691	77
178032	0.1155	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.63	gold quality
lower esophagus mucosa	UBERON:0035834	92.38	gold quality
ectocervix	UBERON:0012249	91.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.76	gold quality
endocervix	UBERON:0000458	89.13	gold quality
heart left ventricle	UBERON:0002084	86.87	gold quality
body of uterus	UBERON:0009853	86.33	gold quality
uterine cervix	UBERON:0000002	86.13	gold quality
cardiac ventricle	UBERON:0002082	85.96	gold quality
right atrium auricular region	UBERON:0006631	84.38	gold quality
vagina	UBERON:0000996	84.03	gold quality
cardiac atrium	UBERON:0002081	83.72	gold quality
stromal cell of endometrium	CL:0002255	83.63	gold quality
esophagus mucosa	UBERON:0002469	83.63	gold quality
heart	UBERON:0000948	82.72	gold quality
gastrocnemius	UBERON:0001388	81.44	gold quality
muscle of leg	UBERON:0001383	81.10	gold quality
ascending aorta	UBERON:0001496	80.82	gold quality
thoracic aorta	UBERON:0001515	80.69	gold quality
left uterine tube	UBERON:0001303	80.53	gold quality
smooth muscle tissue	UBERON:0001135	80.43	gold quality
tibial nerve	UBERON:0001323	80.17	gold quality
descending thoracic aorta	UBERON:0002345	79.48	gold quality
esophagus	UBERON:0001043	78.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.07	silver quality
small intestine Peyer’s patch	UBERON:0003454	76.66	gold quality
right coronary artery	UBERON:0001625	76.55	gold quality
left coronary artery	UBERON:0001626	75.64	gold quality
myometrium	UBERON:0001296	75.56	gold quality
small intestine	UBERON:0002108	75.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting ADAMTSL5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665

Literature-anchored findings (GeneRIF, showing 3)

• ADAMTSL5 could have a role in modulating microfibril functions. (PMID:23010571)
• Chemoresistant B-ALL patients are associated with increased methylation in ADAMTSL5 and CDH11. (PMID:28292214)
• Circular RNA circPFKP suppresses the proliferation and metastasis of gastric cancer cell via sponging miR-644 and regulating ADAMTSL5 expression. (PMID:35587154)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamtsl5	ENSDARG00000052118
mus_musculus	Adamtsl5	ENSMUSG00000043822
rattus_norvegicus	Adamtsl5	ENSRNOG00000033787

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

ADAMTS-like protein 5 — Q6ZMM2 (reviewed: Q6ZMM2)

Alternative names: Thrombospondin type-1 domain-containing protein 6

All UniProt accessions (6): A0A087WVY8, A0A087WZI4, A0A087X1N9, K7ELV0, Q0VD77, X6R4H8

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in modulation of fibrillin microfibrils in the extracellular matrix (ECM).

Subunit / interactions. Interacts with heparin, FBN1 and FBN2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Proteolytically cleaved to release a C-terminal fragment containing the NTR domain. Contains at least one additional N-linked glycosylation site.

Miscellaneous. Major. Minor.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMM2-1	1	yes
Q6ZMM2-2	2

RefSeq proteins (2): NP_001354126, NP_998769* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001134	Netrin_domain	Domain
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR010294	ADAMTS_spacer1	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR018933	Netrin_module_non-TIMP	Domain
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF01759, PF05986, PF19236

UniProt features (15 total): disulfide bond 6, domain 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMM2-F1	83.32	0.54

Functional residue map

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

Disulfide bonds (6): 360–425, 363–427, 377–479, 57–91, 61–96, 72–81

Glycosylation sites (1): 218

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins

MSigDB gene sets: 101 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, CGGAARNGGCNG_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOMF_HEPARIN_BINDING, TGACCTTG_SF1_Q6, chr19p13, SCGGAAGY_ELK1_02, GOMF_SULFUR_COMPOUND_BINDING, GOMF_EXTRACELLULAR_MATRIX_BINDING, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP

GO Biological Process (1): extracellular matrix organization (GO:0030198)

GO Molecular Function (3): heparin binding (GO:0008201), microfibril binding (GO:0050436), protein binding (GO:0005515)

GO Cellular Component (3): microfibril (GO:0001527), extracellular region (GO:0005576), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular structure organization	1
external encapsulating structure organization	1
glycosaminoglycan binding	1
sulfur compound binding	1
extracellular matrix binding	1
binding	1
elastic fiber	1
supramolecular fiber	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTSL5	FBN2	P35556	757
ADAMTSL5	FBN1	P35555	690
ADAMTSL5	PLA2G4D	Q86XP0	685
ADAMTSL5	CAMP	P49913	644
ADAMTSL5	TMEM184B	Q9Y519	572
ADAMTSL5	HLA-C	P04222	570
ADAMTSL5	DOK4	Q8TEW6	549
ADAMTSL5	CD8A	P01732	540
ADAMTSL5	ADAM33	Q9BZ11	454
ADAMTSL5	CARD14	Q9BXL6	434
ADAMTSL5	ADAM11	O75078	422
ADAMTSL5	KRT17	Q04695	419
ADAMTSL5	TPBG	Q13641	419
ADAMTSL5	PKP4	Q99569	392
ADAMTSL5	ADAMDEC1	O15204	386

IntAct

10 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	ADAMTSL5	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ADAMTSL5	psi-mi:“MI:0915”(physical association)	0.560
FHL5	ADAMTSL5	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL5	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.000
ADAMTSL5	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
ADAMTSL5	FHL5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ADAMTSL5 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), ADAMTSL5 (Synthetic Lethality), ADAMTSL5 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP5-9 (Two-hybrid), ADAMTSL5 (Affinity Capture-RNA), ADAMTSL5 (Affinity Capture-RNA)

ESM2 similar proteins: A4FV98, A5PK51, A6NDG6, E1BE10, O00587, O35595, O95294, P60487, Q12788, Q17QS4, Q1JPJ0, Q2T9S4, Q2TBI8, Q32NY4, Q3T063, Q3ZBF9, Q501J2, Q5E9V4, Q5F4B1, Q5IS64, Q5SUV1, Q5T9C9, Q6AYG0, Q6AYR8, Q6XQN1, Q6XQN6, Q6ZMM2, Q80US4, Q8BNV1, Q8BZG5, Q8CC86, Q8IZ69, Q8N9H8, Q8NE01, Q8R2H9, Q8TCT1, Q8VCA8, Q8VD52, Q969S8, Q96AZ1

Diamond homologs: A2VEC9, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXF5, D3YXG0, D3Z7H8, D3ZTD8, E9Q6D8, F1LW30, G1FC92, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O95185, O95450, P07358, P07996, P10643, P11680, P13671, P27918, P35440, P35441, P35442, P35448, P48960, P55314, P57110, P58397, P59384, P61134, P61135

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2279 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1507543:ACAT:A	donor_gain	1.0000
19:1507544:CATC:C	donor_gain	1.0000
19:1507546:T:TA	donor_gain	1.0000
19:1508441:A:AC	donor_gain	1.0000
19:1508442:C:CC	donor_gain	1.0000
19:1508442:CAAGG:C	donor_gain	1.0000
19:1508468:C:CA	donor_gain	1.0000
19:1510144:ACT:A	donor_loss	1.0000
19:1510145:CTC:C	donor_loss	1.0000
19:1510146:TCACC:T	donor_loss	1.0000
19:1510147:C:CG	donor_loss	1.0000
19:1510148:A:T	donor_loss	1.0000
19:1510148:AC:A	donor_gain	1.0000
19:1510148:ACC:A	donor_gain	1.0000
19:1510148:ACCC:A	donor_gain	1.0000
19:1510148:ACCCC:A	donor_gain	1.0000
19:1510149:C:CT	donor_loss	1.0000
19:1510149:CC:C	donor_gain	1.0000
19:1510149:CCC:C	donor_gain	1.0000
19:1510149:CCCC:C	donor_gain	1.0000
19:1510149:CCCCC:C	donor_gain	1.0000
19:1510168:A:AC	donor_gain	1.0000
19:1510169:C:CC	donor_gain	1.0000
19:1510366:A:AC	donor_gain	1.0000
19:1510367:C:CC	donor_gain	1.0000
19:1510729:CCCTA:C	acceptor_gain	1.0000
19:1510730:CCTAC:C	acceptor_gain	1.0000
19:1510731:CTA:C	acceptor_gain	1.0000
19:1512958:CTTA:C	donor_loss	1.0000
19:1512960:TA:T	donor_loss	1.0000

AlphaMissense

3025 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000248511 (19:1509098 A>G), RS1000387171 (19:1514991 AG>A), RS1000662902 (19:1513419 C>A,T), RS1000732323 (19:1514618 T>C), RS1000771630 (19:1509307 C>T), RS1000855430 (19:1507856 T>A,C), RS1000979041 (19:1512925 C>A), RS1001426906 (19:1504774 A>T), RS1001492253 (19:1509444 C>G), RS1001495992 (19:1507648 G>T), RS1001604607 (19:1504800 C>T), RS1001762323 (19:1509424 A>C), RS1001864465 (19:1513512 C>A,T), RS1001874263 (19:1513694 G>A,C), RS1002330223 (19:1507890 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects expression, increases reaction, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol A	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
beta-lapachone	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery