HHATL

Summary

HHATL (hedgehog acyltransferase like, HGNC:13242) is a protein-coding gene on chromosome 3p22.1, encoding Protein-cysteine N-palmitoyltransferase HHAT-like protein (Q9HCP6). Negatively regulates N-terminal palmitoylation of SHH by HHAT/SKN.

Predicted to be involved in negative regulation of N-terminal protein palmitoylation. Located in perinuclear region of cytoplasm.

Source: NCBI Gene 57467 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_020707

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13242
Approved symbol	HHATL
Name	hedgehog acyltransferase like
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	MG56, KIAA1173, OACT3, MSTP002, MBOAT3
Ensembl gene	ENSG00000010282
Ensembl biotype	protein_coding
OMIM	608116
Entrez	57467

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 43 protein_coding, 4 retained_intron

ENST00000310417, ENST00000416756, ENST00000417472, ENST00000426666, ENST00000441594, ENST00000442469, ENST00000455195, ENST00000457462, ENST00000466007, ENST00000480939, ENST00000490003, ENST00000497000, ENST00000888283, ENST00000888284, ENST00000888285, ENST00000888286, ENST00000888287, ENST00000888288, ENST00000888289, ENST00000888290, ENST00000888291, ENST00000888292, ENST00000888293, ENST00000888294, ENST00000888295, ENST00000888296, ENST00000888297, ENST00000888298, ENST00000888299, ENST00000888300, ENST00000888301, ENST00000888302, ENST00000888303, ENST00000888304, ENST00000942111, ENST00000942112, ENST00000942113, ENST00000942114, ENST00000942115, ENST00000942116, ENST00000942117, ENST00000942118, ENST00000942119, ENST00000942120, ENST00000942121, ENST00000942122, ENST00000942123

RefSeq mRNA: 1 — MANE Select: NM_020707 NM_020707

CCDS: CCDS2704

Canonical transcript exons

ENST00000441594 — 12 exons

Exon	Start	End
ENSE00000825809	42697001	42697145
ENSE00000825810	42697508	42697679
ENSE00000825811	42698142	42698351
ENSE00001596849	42699032	42699145
ENSE00001658460	42702579	42702798
ENSE00001685839	42693617	42693818
ENSE00002686529	42696842	42696877
ENSE00003513183	42692663	42692875
ENSE00003527261	42700721	42700839
ENSE00003542023	42699758	42699825
ENSE00003585385	42693077	42693218
ENSE00003661536	42698708	42698902

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 99.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.8880 / max 814.1123, expressed in 157 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41809	2.8223	127
41810	2.3370	122
41811	1.2314	111
41808	0.7330	106
41806	0.6537	86
41804	0.0534	27
41805	0.0425	28
41807	0.0148	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.77	gold quality
apex of heart	UBERON:0002098	99.75	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.54	gold quality
spinal cord	UBERON:0002240	99.44	gold quality
cardiac atrium	UBERON:0002081	99.38	gold quality
right atrium auricular region	UBERON:0006631	99.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.14	gold quality
gastrocnemius	UBERON:0001388	99.08	gold quality
heart left ventricle	UBERON:0002084	98.95	gold quality
cardiac ventricle	UBERON:0002082	98.94	gold quality
myocardium	UBERON:0002349	98.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.65	gold quality
heart right ventricle	UBERON:0002080	98.59	gold quality
substantia nigra	UBERON:0002038	98.58	gold quality
midbrain	UBERON:0001891	98.36	gold quality
inferior vagus X ganglion	UBERON:0005363	98.36	gold quality
skeletal muscle tissue	UBERON:0001134	98.26	gold quality
quadriceps femoris	UBERON:0001377	98.10	gold quality
vastus lateralis	UBERON:0001379	98.06	gold quality
putamen	UBERON:0001874	97.80	gold quality
deltoid	UBERON:0001476	97.72	gold quality
lateral globus pallidus	UBERON:0002476	97.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.70	gold quality
tibialis anterior	UBERON:0001385	97.64	gold quality
biceps brachii	UBERON:0001507	97.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.52	gold quality
amygdala	UBERON:0001876	97.39	gold quality
subthalamic nucleus	UBERON:0001906	97.16	gold quality
right frontal lobe	UBERON:0002810	97.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	37.14
E-ANND-3	no	2.40

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• KIAA1173 gene is highly expressed in normal skin, but it becomes down-regulated in skin squamous cell carcinoma. (PMID:20646595)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hhatlb	ENSDARG00000005139
danio_rerio	hhatla	ENSDARG00000039051
mus_musculus	Hhatl	ENSMUSG00000032523
rattus_norvegicus	Hhatl	ENSRNOG00000019404

Paralogs (1): HHAT (ENSG00000054392)

Protein

Protein identifiers

Protein-cysteine N-palmitoyltransferase HHAT-like protein — Q9HCP6 (reviewed: Q9HCP6)

Alternative names: Glycerol uptake/transporter homolog, Hedgehog acyltransferase-like protein

All UniProt accessions (7): Q9HCP6, C9JEF1, C9JHL0, C9JJ25, C9JKQ1, C9JL39, H7C1Q3

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates N-terminal palmitoylation of SHH by HHAT/SKN.

Subunit / interactions. Interacts with SHH.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Heart-specific.

Similarity. Belongs to the membrane-bound acyltransferase family. HHAT subfamily.

RefSeq proteins (1): NP_065758* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004299	MBOAT_fam	Family
IPR051085	MB_O-acyltransferase	Family

Pfam: PF03062

UniProt features (12 total): transmembrane region 8, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCP6-F1	91.03	0.69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): RNGTGGGC_UNKNOWN, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, NFKB_Q6, NFKB_C, IRF7_01, TGCTGAY_UNKNOWN, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, chr3p22, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (2): regulation of protein modification process (GO:0031399), negative regulation of N-terminal protein palmitoylation (GO:0060262)

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

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
protein modification process	1
regulation of protein metabolic process	1
N-terminal protein palmitoylation	1
regulation of N-terminal protein palmitoylation	1
negative regulation of protein lipidation	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HHATL	B3GNT9	Q6UX72	491
HHATL	QRICH1	Q2TAL8	477
HHATL	MBOAT2	Q6ZWT7	459
HHATL	MBOAT4	Q96T53	408
HHATL	EXOSC1	Q9Y3B2	401
HHATL	FAM241B	Q96D05	392
HHATL	LPCAT3	Q6P1A2	385
HHATL	EEIG2	Q5T8I3	368
HHATL	ANKRD39	Q53RE8	366
HHATL	ANKRD23	Q86SG2	364
HHATL	ZPBP2	Q6X784	362
HHATL	KLHL38	Q2WGJ6	359
HHATL	ASB12	Q8WXK4	356
HHATL	LRRTM3	Q86VH5	336
HHATL	AASDH	Q4L235	335

IntAct

54 interactions, top by confidence:

A	B	Type	Score
CXCL16	HHATL	psi-mi:“MI:0915”(physical association)	0.560
HHATL	TMX2	psi-mi:“MI:0915”(physical association)	0.560
HHATL	PVR	psi-mi:“MI:0915”(physical association)	0.560
HHATL	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	HHATL	psi-mi:“MI:0915”(physical association)	0.560
CISD2	HHATL	psi-mi:“MI:0915”(physical association)	0.560
MUC1	HHATL	psi-mi:“MI:0915”(physical association)	0.560
MILR1	HHATL	psi-mi:“MI:0915”(physical association)	0.560
HHATL	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
PVR	HHATL	psi-mi:“MI:0915”(physical association)	0.560
GPR152	HHATL	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	HHATL	psi-mi:“MI:0915”(physical association)	0.560
SUSD3	HHATL	psi-mi:“MI:0915”(physical association)	0.560
GPX8	HHATL	psi-mi:“MI:0915”(physical association)	0.560
ARLN	HHATL	psi-mi:“MI:0915”(physical association)	0.560
CPLX4	HHATL	psi-mi:“MI:0915”(physical association)	0.560
FNDC9	HHATL	psi-mi:“MI:0915”(physical association)	0.560
HHATL	ACOT1	psi-mi:“MI:0915”(physical association)	0.400
HHATL	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
HHATL	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
HHATL	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
HHATL	CACNA1A	psi-mi:“MI:0915”(physical association)	0.370
HHATL	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000
HHATL	AMIGO1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): HHATL (Synthetic Lethality), PVR (Two-hybrid), FKBP7 (Two-hybrid), FAM209A (Two-hybrid), ERGIC3 (Two-hybrid), CISD2 (Two-hybrid), SUSD3 (Two-hybrid), CXCL16 (Two-hybrid), C4orf3 (Two-hybrid), GPX8 (Two-hybrid), CPLX4 (Two-hybrid), FNDC9 (Two-hybrid), GPR152 (Two-hybrid), AMIGO1 (Two-hybrid), MUC1 (Two-hybrid)

ESM2 similar proteins: A0A8C2M425, A1A5Z0, A5D6W6, A7YWN2, B0BNG2, B2MVP8, D2HSA6, O19133, O42153, O42154, O75908, O77759, O88908, P35575, P35576, P43428, Q148G2, Q19KA1, Q29RU6, Q4FZU9, Q5E9R1, Q5KR61, Q5RKL5, Q5XK03, Q658P3, Q6AX73, Q6AZ83, Q6GQ62, Q6NSQ9, Q7TPN3, Q7TQM4, Q810K3, Q8BJ52, Q8CI59, Q8IWX5, Q8R1J1, Q8R2R1, Q8WTR4, Q91V79, Q99PR0

Diamond homologs: Q9D1G3, Q9HCP6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1944 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42692874:CC:C	acceptor_gain	1.0000
3:42692875:CCTG:C	acceptor_gain	1.0000
3:42693071:CCTCA:C	donor_loss	1.0000
3:42693072:CTCA:C	donor_loss	1.0000
3:42693073:TCA:T	donor_loss	1.0000
3:42693074:CACCT:C	donor_loss	1.0000
3:42693075:ACCT:A	donor_loss	1.0000
3:42693076:C:CA	donor_loss	1.0000
3:42693259:C:CT	acceptor_gain	1.0000
3:42693260:A:T	acceptor_gain	1.0000
3:42696839:CAC:C	donor_loss	1.0000
3:42696840:A:AC	donor_gain	1.0000
3:42696840:A:C	donor_loss	1.0000
3:42696841:C:CT	donor_gain	1.0000
3:42696841:CTTG:C	donor_gain	1.0000
3:42696878:C:CC	acceptor_gain	1.0000
3:42696999:A:AC	donor_gain	1.0000
3:42697000:C:CC	donor_gain	1.0000
3:42697000:CG:C	donor_gain	1.0000
3:42698136:CCTCA:C	donor_loss	1.0000
3:42698137:CTCAC:C	donor_loss	1.0000
3:42698138:TCAC:T	donor_loss	1.0000
3:42698139:CACC:C	donor_loss	1.0000
3:42698140:A:AG	donor_loss	1.0000
3:42698141:C:CA	donor_loss	1.0000
3:42698319:T:C	acceptor_gain	1.0000
3:42699026:GCTCA:G	donor_loss	1.0000
3:42699027:CTCA:C	donor_loss	1.0000
3:42699028:TCACC:T	donor_loss	1.0000
3:42699029:CACCT:C	donor_loss	1.0000

AlphaMissense

3284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42698268:G:C	S189R	0.998
3:42698268:G:T	S189R	0.998
3:42698270:T:G	S189R	0.998
3:42693746:A:C	F373L	0.995
3:42693746:A:T	F373L	0.995
3:42693748:A:G	F373L	0.995
3:42693700:A:G	W389R	0.994
3:42693700:A:T	W389R	0.994
3:42696871:A:C	F339L	0.994
3:42696871:A:T	F339L	0.994
3:42696873:A:G	F339L	0.994
3:42698160:A:C	F225L	0.994
3:42698160:A:T	F225L	0.994
3:42698162:A:G	F225L	0.994
3:42697090:A:C	F307L	0.993
3:42697090:A:T	F307L	0.993
3:42697092:A:G	F307L	0.993
3:42699127:A:G	W65R	0.993
3:42699127:A:T	W65R	0.993
3:42693686:G:C	N393K	0.991
3:42693686:G:T	N393K	0.991
3:42696869:T:A	D340V	0.991
3:42697105:C:A	K302N	0.991
3:42697105:C:G	K302N	0.991
3:42699145:C:G	D59H	0.991
3:42693129:G:C	S446R	0.990
3:42693129:G:T	S446R	0.990
3:42693131:T:G	S446R	0.990
3:42696852:A:G	W346R	0.990
3:42696852:A:T	W346R	0.990

dbSNP variants (sampled 300 via entrez): RS1000334203 (3:42695433 T>C), RS1000407742 (3:42695738 G>A), RS1000455196 (3:42703610 G>A), RS1000654399 (3:42698386 G>A,C), RS1000728499 (3:42692695 G>A), RS1000760096 (3:42692469 G>A), RS1001272019 (3:42698835 A>G), RS1001338234 (3:42700031 T>C,G), RS1001345083 (3:42704155 G>A), RS1001370926 (3:42695622 TG>T,TGG), RS1003041566 (3:42697230 G>C,T), RS1003352159 (3:42697439 C>T), RS1003357806 (3:42701525 C>A), RS1003378415 (3:42702234 G>A), RS1003431328 (3:42701751 G>A)

Disease associations

OMIM: gene MIM:608116 | 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: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	2
sodium arsenite	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diazinon	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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