LHFPL6

Summary

LHFPL6 (LHFPL tetraspan subfamily member 6, HGNC:6586) is a protein-coding gene on chromosome 13q13.3-q14.11, encoding LHFPL tetraspan subfamily member 6 protein (Q9Y693).

This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. This gene is fused to a high-mobility group gene in a translocation-associated lipoma. Mutations in another LHFP-like gene result in deafness in humans and mice. Alternatively spliced transcript variants have been found; however, their full-length nature is not known.

Source: NCBI Gene 10186 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_005780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6586
Approved symbol	LHFPL6
Name	LHFPL tetraspan subfamily member 6
Location	13q13.3-q14.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC22429
Ensembl gene	ENSG00000183722
Ensembl biotype	protein_coding
OMIM	606710
Entrez	10186

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000379589, ENST00000495922, ENST00000648377, ENST00000855017, ENST00000855018, ENST00000965821

RefSeq mRNA: 1 — MANE Select: NM_005780 NM_005780

CCDS: CCDS9369

Canonical transcript exons

ENST00000379589 — 4 exons

Exon	Start	End
ENSE00001327909	39378428	39378526
ENSE00001481720	39342892	39344054
ENSE00001481735	39600832	39601390
ENSE00001481736	39602883	39603193

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.4587 / max 597.0157, expressed in 1471 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136890	20.5417	1443
136891	1.8516	957
136884	1.3848	593
136883	0.8999	480
136886	0.8288	361
136885	0.7804	345
136892	0.1715	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	98.74	gold quality
calcaneal tendon	UBERON:0003701	98.73	gold quality
synovial joint	UBERON:0002217	98.49	gold quality
right coronary artery	UBERON:0001625	98.31	gold quality
superficial temporal artery	UBERON:0001614	98.10	gold quality
saphenous vein	UBERON:0007318	98.10	gold quality
tibial nerve	UBERON:0001323	98.09	gold quality
cerebellar vermis	UBERON:0004720	98.07	gold quality
blood vessel layer	UBERON:0004797	98.07	gold quality
omental fat pad	UBERON:0010414	98.01	gold quality
left coronary artery	UBERON:0001626	98.00	gold quality
peritoneum	UBERON:0002358	98.00	gold quality
descending thoracic aorta	UBERON:0002345	97.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.95	gold quality
coronary artery	UBERON:0001621	97.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.94	gold quality
pericardium	UBERON:0002407	97.88	gold quality
mammary duct	UBERON:0001765	97.80	gold quality
popliteal artery	UBERON:0002250	97.80	gold quality
tibial artery	UBERON:0007610	97.80	gold quality
choroid plexus epithelium	UBERON:0003911	97.76	gold quality
aorta	UBERON:0000947	97.73	gold quality
adipose tissue	UBERON:0001013	97.69	gold quality
thoracic aorta	UBERON:0001515	97.64	gold quality
ascending aorta	UBERON:0001496	97.61	gold quality
connective tissue	UBERON:0002384	97.52	gold quality
trigeminal ganglion	UBERON:0001675	97.51	gold quality
dorsal root ganglion	UBERON:0000044	97.47	gold quality
left uterine tube	UBERON:0001303	97.37	gold quality
tendon of biceps brachii	UBERON:0008188	97.30	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	702.66
E-MTAB-10662	yes	315.45
E-MTAB-8410	yes	51.48
E-MTAB-6701	yes	45.29
E-GEOD-135922	yes	33.67
E-HCAD-10	yes	32.16
E-HCAD-35	yes	21.64
E-HCAD-4	yes	19.35
E-HCAD-1	yes	16.81
E-MTAB-6678	yes	16.33
E-HCAD-5	yes	14.41
E-MTAB-5061	yes	10.86
E-CURD-119	yes	10.68
E-GEOD-81547	yes	10.51
E-CURD-46	yes	9.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

93 targeting LHFPL6, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-539-5P	99.93	70.30	2855

Literature-anchored findings (GeneRIF, showing 2)

• The authors present an overview of the LHFP gene family in mouse and humans (PMID:15905332)
• Amplification of the LHFP gene is associated with mesenchymal differentiation in gliosarcoma. (PMID:22538188)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lhfpl6	ENSDARG00000004363
mus_musculus	Lhfpl6	ENSMUSG00000048332
rattus_norvegicus	Lhfpl6	ENSRNOG00000014153

Paralogs (6): LHFPL2 (ENSG00000145685), LHFPL4 (ENSG00000156959), LHFPL1 (ENSG00000182508), LHFPL3 (ENSG00000187416), LHFPL5 (ENSG00000197753), LHFPL7 (ENSG00000206069)

Protein

Protein identifiers

LHFPL tetraspan subfamily member 6 protein — Q9Y693 (reviewed: Q9Y693)

Alternative names: Lipoma HMGIC fusion partner

All UniProt accessions (1): Q9Y693

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Pancreas, kidney, skeletal muscle, liver, lung brain, heart, colon, small intestine, uterus, testis, prostate, thymus, spleen and placenta.

Disease relevance. A chromosomal aberration involving LHFP is associated with a subclass of benign mesenchymal tumors known as lipomas. Translocation t(12;13)(q13-q15;q12) with HMGA2 is shown in lipomas.

Similarity. Belongs to the LHFP family.

RefSeq proteins (1): NP_005771* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019372	LHFPL	Family

Pfam: PF10242

UniProt features (5 total): transmembrane region 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y693-F1	91.70	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 181 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, AAAYRNCTG_UNKNOWN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, ONKEN_UVEAL_MELANOMA_UP, WTGAAAT_UNKNOWN, TGIF_01, USF_02, HUANG_FOXA2_TARGETS_UP, chr13q14, RIZKI_TUMOR_INVASIVENESS_3D_UP, SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP, GARY_CD5_TARGETS_UP, DIAZ_CHRONIC_MYELOGENOUS_LEUKEMIA_DN

GO Biological Process (0):

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LHFPL6	F5H6H0	F5H6H0	818
LHFPL6	LPP	Q93052	649
LHFPL6	COX6C	P09669	639
LHFPL6	CCNB1IP1	Q9NPC3	636
LHFPL6	RAD51B	O15315	610
LHFPL6	COG6	Q9Y2V7	578
LHFPL6	COL11A2	P13942	527
LHFPL6	ALDH2	P05091	468
LHFPL6	MRPS31	Q92665	459
LHFPL6	NFIB	O00712	443
LHFPL6	XRCC5	P13010	435
LHFPL6	PRKDC	P78527	424
LHFPL6	EBF1	Q9UH73	421
LHFPL6	OR4E2	Q8NGC2	400
LHFPL6	OR10Z1	Q8NGY1	397

IntAct

2 interactions, top by confidence:

A	B	Type	Score
LHFPL6	TNFRSF10C	psi-mi:“MI:0914”(association)	0.350
LHFPL6	IFITM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): TNFRSF10C (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), IFITM3 (Affinity Capture-MS), PTRH2 (Affinity Capture-MS)

ESM2 similar proteins: B3SHH9, F6V1J6, H3BS89, M0RAS4, P54825, P55344, P56563, P62955, P62956, P62957, Q06432, Q13635, Q17R16, Q1L8F4, Q3KRC4, Q4R4I5, Q5BJS2, Q5H8A4, Q5U4E0, Q5ZML7, Q61115, Q68FV0, Q6GQW0, Q6PFT6, Q6QRN8, Q6ZVK1, Q7TNR6, Q7TSY2, Q7Z6J6, Q7Z7J7, Q86UP9, Q8BHH9, Q8BM86, Q8NBL3, Q8NBT3, Q8NCR0, Q8VHW2, Q8VHW4, Q8VHW5, Q8VHW8

Diamond homologs: Q5BJS2, Q5PRC1, Q6P0C6, Q80SV1, Q80WE5, Q86WI0, Q8BM86, Q9Y693, Q6DHB5, Q17R16, Q4KL25, Q5PPI7, Q5U4E0, Q66IV3, Q7TSY2, Q7Z7J7, Q7ZZL8, Q86UP9, Q8TAF8, Q9CTN8, Q6ICI0, Q6ZUX7, Q8BGA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2618 predictions. Top by Δscore:

Variant	Effect	Δscore
13:39344050:CTTCC:C	acceptor_gain	1.0000
13:39344052:TCCCT:T	acceptor_loss	1.0000
13:39344053:CC:C	acceptor_gain	1.0000
13:39344054:CC:C	acceptor_gain	1.0000
13:39344055:C:A	acceptor_loss	1.0000
13:39344055:C:CC	acceptor_gain	1.0000
13:39344056:T:G	acceptor_loss	1.0000
13:39378421:AGCTT:A	donor_loss	1.0000
13:39378422:GCTTA:G	donor_loss	1.0000
13:39378423:CTTA:C	donor_loss	1.0000
13:39378424:TTACC:T	donor_loss	1.0000
13:39378425:TA:T	donor_loss	1.0000
13:39378426:A:AC	donor_gain	1.0000
13:39378426:AC:A	donor_gain	1.0000
13:39378427:C:CC	donor_gain	1.0000
13:39378427:CC:C	donor_gain	1.0000
13:39378523:AAGCC:A	acceptor_loss	1.0000
13:39378524:AGCCT:A	acceptor_loss	1.0000
13:39378527:CT:C	acceptor_loss	1.0000
13:39378528:T:C	acceptor_loss	1.0000
13:39433449:AAT:A	donor_gain	1.0000
13:39601391:C:CG	acceptor_loss	1.0000
13:39601392:T:A	acceptor_loss	1.0000
13:39602881:A:AC	donor_gain	1.0000
13:39602882:C:CC	donor_gain	1.0000
13:39344051:TTCC:T	acceptor_gain	0.9900
13:39344052:TCC:T	acceptor_gain	0.9900
13:39344053:CCC:C	acceptor_gain	0.9900
13:39378522:CAAGC:C	acceptor_gain	0.9900
13:39378523:AAGC:A	acceptor_gain	0.9900

AlphaMissense

1279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:39600971:C:A	W82C	0.998
13:39600971:C:G	W82C	0.998
13:39600973:A:G	W82R	0.998
13:39600973:A:T	W82R	0.998
13:39378485:A:G	W143R	0.997
13:39378485:A:T	W143R	0.997
13:39378483:C:A	W143C	0.996
13:39378483:C:G	W143C	0.996
13:39601005:T:C	Y71C	0.996
13:39601068:C:G	C50S	0.996
13:39601069:A:T	C50S	0.996
13:39378497:A:C	Y139D	0.995
13:39600943:C:G	G92R	0.995
13:39601069:A:G	C50R	0.995
13:39601074:C:G	R48P	0.995
13:39378457:C:T	C152Y	0.994
13:39600942:C:T	G92D	0.994
13:39601076:G:C	F47L	0.994
13:39601076:G:T	F47L	0.994
13:39601078:A:G	F47L	0.994
13:39601121:C:A	W32C	0.994
13:39601121:C:G	W32C	0.994
13:39601141:C:G	G26R	0.994
13:39601141:C:T	G26R	0.994
13:39601183:A:G	W12R	0.994
13:39601183:A:T	W12R	0.994
13:39601077:A:C	F47C	0.993
13:39601084:C:G	G45R	0.993
13:39601123:A:G	W32R	0.993
13:39601123:A:T	W32R	0.993

dbSNP variants (sampled 300 via entrez): RS1000014473 (13:39550763 A>G), RS1000026706 (13:39546212 C>T), RS1000064772 (13:39438789 T>A), RS1000070060 (13:39381050 T>A), RS1000072351 (13:39402795 G>A), RS1000098973 (13:39587785 T>C), RS1000111257 (13:39447368 T>A), RS1000125060 (13:39461549 G>C), RS1000140540 (13:39502583 T>C), RS1000146531 (13:39357027 C>A,T), RS1000165247 (13:39551757 AT>A,ATT), RS1000169951 (13:39586328 T>C), RS1000176111 (13:39491066 T>C), RS1000181771 (13:39463508 T>C), RS1000206896 (13:39508446 T>C)

Disease associations

OMIM: gene MIM:606710 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001530_10	Hippocampal atrophy	2.000000e-08
GCST001949_16	Preeclampsia	5.000000e-06
GCST004813_3	Laterality in neovascular age-related macular degeneration	1.000000e-06
GCST009798_42	Asthma	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy
EFO:0008372	laterality measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	8
methylmercuric chloride	increases expression	3
trichostatin A	affects cotreatment, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Arsenic Trioxide	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Cadmium	decreases expression, increases abundance	2
Cisplatin	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	increases expression	2
Silicon Dioxide	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
terbufos	increases methylation	1
cinnamaldehyde	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	increases expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3U4	SEES3-1V human LHFP, clone1	Embryonic stem cell	Male
CVCL_A3U5	SEES3-1V human LHFP, clone2	Embryonic stem cell	Male
CVCL_A3U6	SEES3-1V human LHFP, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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