LIMS4

Summary

LIMS4 (LIM zinc finger domain containing 4, HGNC:39941) is a protein-coding gene on chromosome 2q13, encoding LIM and senescent cell antigen-like-containing domain protein 4 (P0CW20).

Predicted to enable metal ion binding activity. Predicted to be located in cytoplasm; focal adhesion; and plasma membrane.

Source: NCBI Gene 100288695 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 11 total — 2 pathogenic
• MANE Select transcript: NM_001371340

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:39941
Approved symbol	LIMS4
Name	LIM zinc finger domain containing 4
Location	2q13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000256671
Ensembl biotype	protein_coding
Entrez	100288695

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000413601, ENST00000480598, ENST00000632758, ENST00000632897, ENST00000633364

RefSeq mRNA: 2 — MANE Select: NM_001371340 NM_001205288, NM_001371340

CCDS: CCDS54387, CCDS92838

Canonical transcript exons

ENST00000632897 — 10 exons

Exon	Start	End
ENSE00003700306	110468095	110468254
ENSE00003775547	110454851	110455000
ENSE00003775603	110472597	110472816
ENSE00003777348	110445883	110446886
ENSE00003778116	110451864	110452014
ENSE00003779057	110447085	110447160
ENSE00003780036	110455435	110455555
ENSE00003781373	110457030	110457096
ENSE00003781395	110451161	110451253
ENSE00003782474	110449819	110449867

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 90.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1703 / max 13.5622, expressed in 96 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
202337	0.1703	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	90.94	gold quality
ascending aorta	UBERON:0001496	90.28	gold quality
thoracic aorta	UBERON:0001515	90.23	gold quality
endometrium	UBERON:0001295	89.83	gold quality
right uterine tube	UBERON:0001302	87.58	gold quality
stromal cell of endometrium	CL:0002255	85.09	gold quality
right coronary artery	UBERON:0001625	82.67	gold quality
left coronary artery	UBERON:0001626	82.38	gold quality
tibial artery	UBERON:0007610	82.19	gold quality
popliteal artery	UBERON:0002250	82.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.06	gold quality
right adrenal gland cortex	UBERON:0035827	79.38	gold quality
left adrenal gland cortex	UBERON:0035825	79.24	gold quality
fallopian tube	UBERON:0003889	79.19	gold quality
left adrenal gland	UBERON:0001234	78.53	gold quality
right adrenal gland	UBERON:0001233	77.89	gold quality
adrenal gland	UBERON:0002369	77.25	gold quality
gastrocnemius	UBERON:0001388	76.04	gold quality
metanephros cortex	UBERON:0010533	75.35	gold quality
muscle of leg	UBERON:0001383	74.28	gold quality
right atrium auricular region	UBERON:0006631	73.95	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.92	gold quality
adrenal tissue	UBERON:0018303	73.69	gold quality
skeletal muscle tissue	UBERON:0001134	73.62	gold quality
left ovary	UBERON:0002119	73.23	gold quality
islet of Langerhans	UBERON:0000006	73.00	gold quality
right ovary	UBERON:0002118	72.72	gold quality
adipose tissue	UBERON:0001013	72.41	gold quality
ovary	UBERON:0000992	72.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.00	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	16.38
E-MTAB-6678	yes	8.92
E-ANND-3	yes	5.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting LIMS4, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-711	96.60	65.75	528
HSA-MIR-4791	96.51	67.76	659
HSA-MIR-6856-3P	96.47	66.27	781

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	lims2	ENSDARG00000014976
danio_rerio	lims1	ENSDARG00000026985
mus_musculus	Lims1	ENSMUSG00000019920
rattus_norvegicus	Lims1	ENSRNOG00000037765
drosophila_melanogaster	stck	FBGN0020249
drosophila_melanogaster	Zasp67	FBGN0036044
caenorhabditis_elegans		WBGENE00004030
caenorhabditis_elegans		WBGENE00006826

Paralogs (3): LIMS2 (ENSG00000072163), LIMS1 (ENSG00000169756), LIMS3 (ENSG00000256977)

Protein

Protein identifiers

LIM and senescent cell antigen-like-containing domain protein 4 — P0CW20 (reviewed: P0CW20)

Alternative names: LIM and senescent cell antigen-like-containing domain protein 3-like

All UniProt accessions (2): P0CW20, A0A0J9YXC7

RefSeq proteins (2): NP_001192217, NP_001358269* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR017351	PINCH-1-4-like	Family

Pfam: PF00412

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CW20-F1	72.74	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): MIR4492, MIR4524A_5P, MIR4524B_5P, MIR4699_5P, GSE13306_LAMINA_PROPRIA_VS_SPLEEN_TREG_DN, GSE13306_TREG_VS_TCONV_SPLEEN_DN, MIR1287_5P, GSE14308_TH2_VS_TH1_DN, GSE14308_TH2_VS_TH17_DN, GSE14308_TH2_VS_NATURAL_TREG_DN, GSE17721_POLYIC_VS_CPG_24H_BMDC_DN, GSE17721_0.5H_VS_4H_CPG_BMDC_DN, GSE20366_TREG_VS_NAIVE_CD4_TCELL_HOMEOSTATIC_CONVERSION_DN, GSE20715_WT_VS_TLR4_KO_48H_OZONE_LUNG_UP, GSE20715_0H_VS_48H_OZONE_LUNG_UP

GO Biological Process (2): cell surface receptor signaling pathway (GO:0007166), positive regulation of signal transduction (GO:0009967)

GO Molecular Function (3): metal ion binding (GO:0046872), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
cation binding	1
cytoskeletal protein binding	1
binding	1
membrane	1
cell periphery	1
cell-substrate junction	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

38 interactions, top by confidence:

A	B	Type	Score
LIMS4	BCL6	psi-mi:“MI:0915”(physical association)	0.720
BCL6	LIMS4	psi-mi:“MI:0915”(physical association)	0.720
LIMS4	GMCL2	psi-mi:“MI:0915”(physical association)	0.560
GMCL2	LIMS4	psi-mi:“MI:0915”(physical association)	0.560
CRX	LIMS4	psi-mi:“MI:0915”(physical association)	0.560
LIMS4	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
LIMS4	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
LIMS4	ARID5A	psi-mi:“MI:0915”(physical association)	0.560
LIMS4	C10orf55	psi-mi:“MI:0915”(physical association)	0.560
	LIMS4	psi-mi:“MI:0915”(physical association)	0.560
LIMS4	FAM219A	psi-mi:“MI:0915”(physical association)	0.560
TRIM49C	LIMS4	psi-mi:“MI:0915”(physical association)	0.560
LIMS4	KLHDC7B	psi-mi:“MI:0915”(physical association)	0.560
ECE1	LIMS4	psi-mi:“MI:0915”(physical association)	0.370
LIMS4	CRX	psi-mi:“MI:0915”(physical association)	0.000
LIMS4	RUSC1	psi-mi:“MI:0915”(physical association)	0.000
LIMS4	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.000
LIMS4	ARID5A	psi-mi:“MI:0915”(physical association)	0.000
LIMS4	C10orf55	psi-mi:“MI:0915”(physical association)	0.000
LIMS4		psi-mi:“MI:0915”(physical association)	0.000
LIMS4	FAM219A	psi-mi:“MI:0915”(physical association)	0.000
LIMS4	TRIM49C	psi-mi:“MI:0915”(physical association)	0.000
BCL6	LIMS4	psi-mi:“MI:0915”(physical association)	0.000
LIMS4	KLHDC7B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): LIMS3 (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid), LIMS3 (Two-hybrid), LIMS3L (Two-hybrid)

ESM2 similar proteins: B6H6F3, B8NLZ3, C8VDQ4, E5DG73, G4NEB8, O14448, O42794, O54992, O59922, O95259, P0CW19, P0CW20, P25908, P28348, P32023, P52959, P86244, P93025, Q01386, Q03043, Q0U822, Q14123, Q2QYY8, Q2RBR1, Q2UPB6, Q4IJ84, Q4WCV3, Q4WPU8, Q4WQL0, Q4X1A8, Q5RF96, Q5ZKK1, Q60603, Q63421, Q64338, Q6DC61, Q7S1P9, Q7TX80, Q86ZN7, Q8INB9

Diamond homologs: A5H447, P0CW19, P0CW20, P48059, P50464, Q0VA45, Q15942, Q2KJ33, Q7Z4I7, Q91XD2, Q99JW4, A1Z6W3, A1ZA47, B5DEH0, B7ZUL2, E1BKA3, G5E5X0, O42565, O43294, O60711, O74398, O75112, P25791, P25800, P25801, P36202, P49023, P49024, P50212, P50479, P50480, P53406, P53407, P53408, P53409, P70271, Q06BR1, Q07E40, Q09476, Q174I2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LIMS4	“form complex”	“IPP complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
57545	GRCh38/hg38 2q13(chr2:110025659-110371270)x0	Pathogenic
980469	GRCh37/hg19 2q12.2-13(chr2:107029680-113187742)x1	Pathogenic

SpliceAI

1576 predictions. Top by Δscore:

Variant	Effect	Δscore
2:110446746:CAGA:C	donor_gain	1.0000
2:110446749:A:AC	donor_gain	1.0000
2:110446750:C:CC	donor_gain	1.0000
2:110446750:CTGG:C	donor_gain	1.0000
2:110446778:AT:A	donor_gain	1.0000
2:110446779:T:C	donor_gain	1.0000
2:110447083:A:AC	donor_gain	1.0000
2:110447084:C:CC	donor_gain	1.0000
2:110447158:CCA:C	acceptor_gain	1.0000
2:110447159:CA:C	acceptor_gain	1.0000
2:110447159:CAC:C	acceptor_gain	1.0000
2:110447161:C:CC	acceptor_gain	1.0000
2:110449812:TACTT:T	donor_loss	1.0000
2:110449813:ACTTA:A	donor_loss	1.0000
2:110449814:CT:C	donor_loss	1.0000
2:110449815:TT:T	donor_loss	1.0000
2:110449816:T:TC	donor_loss	1.0000
2:110449817:A:AC	donor_gain	1.0000
2:110449818:C:CC	donor_gain	1.0000
2:110449818:C:CG	donor_loss	1.0000
2:110449818:C:CT	donor_loss	1.0000
2:110449863:AATAG:A	acceptor_gain	1.0000
2:110449864:ATAG:A	acceptor_gain	1.0000
2:110449865:TAG:T	acceptor_gain	1.0000
2:110449865:TAGC:T	acceptor_loss	1.0000
2:110449866:AG:A	acceptor_gain	1.0000
2:110449867:GCTG:G	acceptor_loss	1.0000
2:110449867:GCTGA:G	acceptor_loss	1.0000
2:110449868:C:CC	acceptor_gain	1.0000
2:110449868:CTGAA:C	acceptor_loss	1.0000

AlphaMissense

2681 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:110468143:G:C	F98L	0.992
2:110468143:G:T	F98L	0.992
2:110468145:A:G	F98L	0.992
2:110468200:A:C	F79L	0.991
2:110468200:A:T	F79L	0.991
2:110468202:A:G	F79L	0.991
2:110468201:A:C	F79C	0.988
2:110468201:A:G	F79S	0.987
2:110468148:A:G	C97R	0.985
2:110468147:C:G	C97S	0.984
2:110468148:A:T	C97S	0.984
2:110468157:G:C	H94D	0.981
2:110468144:A:C	F98C	0.980
2:110468160:A:C	Y93D	0.980
2:110468129:C:G	C103S	0.979
2:110468130:A:T	C103S	0.979
2:110468144:A:G	F98S	0.979
2:110468222:C:T	C72Y	0.978
2:110468155:A:C	H94Q	0.977
2:110468155:A:T	H94Q	0.977
2:110468101:G:C	F112L	0.976
2:110468101:G:T	F112L	0.976
2:110468103:A:G	F112L	0.976
2:110468222:C:G	C72S	0.976
2:110468223:A:T	C72S	0.976
2:110468213:C:G	C75S	0.974
2:110468214:A:T	C75S	0.974
2:110468117:A:C	F107C	0.973
2:110468130:A:G	C103R	0.973
2:110468117:A:G	F107S	0.972

dbSNP variants (sampled 300 via entrez): RS1000081983 (2:110402920 T>C), RS1000569775 (2:110373527 G>C), RS1000600939 (2:110374864 C>T), RS1000900036 (2:110419517 G>C), RS1001116240 (2:110397280 T>A), RS1001139445 (2:110418477 G>A), RS1001635768 (2:110456884 TC>T), RS1001674231 (2:110358985 A>T), RS1001760491 (2:110395397 A>G), RS1002120507 (2:110406116 G>A,T), RS1002237472 (2:110366715 T>A), RS1002272319 (2:110368555 C>A,G), RS1002798054 (2:110390061 C>T), RS1003376055 (2:110431826 C>A), RS1003434662 (2:110387972 A>T)

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

1 associations (top):

Study	Trait	p-value
GCST002929_12	Chromium levels	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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