TLCD3B

Summary

TLCD3B (TLC domain containing 3B, HGNC:25295) is a protein-coding gene on chromosome 16p11.2, encoding Ceramide synthase (Q71RH2). Involved in ceramide synthesis.

This gene encodes a transmembrane protein, which may be a likely target of peroxisome proliferator-activated receptor gamma (PPAR-gamma). The product of the orthologous gene in mouse is related to obesity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 83723 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy 22 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 13 total — 3 pathogenic
• Phenotypes (HPO): 26
• MANE Select transcript: NM_031478

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25295
Approved symbol	TLCD3B
Name	TLC domain containing 3B
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434I2117
Ensembl gene	ENSG00000149926
Ensembl biotype	protein_coding
OMIM	615175
Entrez	83723

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000279389, ENST00000380495, ENST00000561666, ENST00000564806, ENST00000567037, ENST00000569508, ENST00000571269, ENST00000934494

RefSeq mRNA: 3 — MANE Select: NM_031478 NM_001318504, NM_001352173, NM_031478

CCDS: CCDS10667, CCDS81967

Canonical transcript exons

ENST00000380495 — 5 exons

Exon	Start	End
ENSE00000993003	30026609	30026843
ENSE00000993004	30025726	30025821
ENSE00001670248	30024427	30025467
ENSE00001782666	30030403	30031271
ENSE00003620505	30029432	30029515

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 96.90.

FANTOM5 (CAGE): breadth broad, TPM avg 10.7180 / max 1035.5718, expressed in 602 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156997	4.7947	280
156999	3.6216	249
157000	0.6449	124
157007	0.5965	283
207830	0.4304	127
156998	0.3345	150
157006	0.0678	29
207829	0.0672	41
157001	0.0618	35
157003	0.0469	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.90	gold quality
cortical plate	UBERON:0005343	96.70	gold quality
right testis	UBERON:0004534	96.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.17	gold quality
ganglionic eminence	UBERON:0004023	96.04	gold quality
embryo	UBERON:0000922	96.03	gold quality
cerebellar hemisphere	UBERON:0002245	95.55	gold quality
cerebellar cortex	UBERON:0002129	95.52	gold quality
cerebellum	UBERON:0002037	94.82	gold quality
vena cava	UBERON:0004087	93.05	gold quality
testis	UBERON:0000473	93.02	gold quality
right frontal lobe	UBERON:0002810	91.55	gold quality
pons	UBERON:0000988	90.92	gold quality
anterior cingulate cortex	UBERON:0009835	89.95	gold quality
kidney epithelium	UBERON:0004819	89.87	silver quality
prefrontal cortex	UBERON:0000451	89.48	gold quality
cerebellar vermis	UBERON:0004720	89.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.00	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.83	gold quality
neocortex	UBERON:0001950	88.82	gold quality
body of tongue	UBERON:0011876	88.77	gold quality
frontal cortex	UBERON:0001870	88.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.25	gold quality
cerebral cortex	UBERON:0000956	87.37	gold quality
amygdala	UBERON:0001876	87.17	gold quality
brain	UBERON:0000955	86.80	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.45	silver quality
nucleus accumbens	UBERON:0001882	86.41	gold quality
parotid gland	UBERON:0001831	86.30	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	952.27
E-HCAD-5	yes	9.19
E-HCAD-10	yes	4.28
E-ANND-3	yes	3.57
E-MTAB-7316	no	30.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

23 targeting TLCD3B, 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-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-6753-5P	94.70	64.08	470
HSA-MIR-4321	92.11	68.79	45
HSA-MIR-3178	89.40	60.05	100
HSA-MIR-4738-5P	87.41	60.29	56
HSA-MIR-10394-3P	85.92	60.60	39

Literature-anchored findings (GeneRIF, showing 1)

• Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy. (PMID:33077892)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tlcd3ba	ENSDARG00000026875
danio_rerio	tlcd3bb	ENSDARG00000074564
mus_musculus	Tlcd3b	ENSMUSG00000058966
rattus_norvegicus	Tlcd3b	ENSRNOG00000019914
drosophila_melanogaster	CG17841	FBGN0028480

Paralogs (5): TLCD4 (ENSG00000152078), TLCD1 (ENSG00000160606), TLCD3A (ENSG00000167695), CLN8 (ENSG00000182372), TLCD2 (ENSG00000185561)

Protein

Protein identifiers

Ceramide synthase — Q71RH2 (reviewed: Q71RH2)

Alternative names: Protein FAM57B, TLC domain-containing protein 3B

All UniProt accessions (6): Q71RH2, F1T0F5, H3BST4, H3BUM7, H3BUS2, I3L180

UniProt curated annotations — full annotation on UniProt →

Function. Involved in ceramide synthesis.

Subcellular location. Golgi apparatus membrane Endoplasmic reticulum membrane.

Tissue specificity. Expressed in testis. Expressed in the retina with higher expression levels in the macular than in the peripheral region.

Disease relevance. Cone-rod dystrophy 22 (CORD22) [MIM:619531] An autosomal recessive form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q71RH2-1	1	yes
Q71RH2-2	2

RefSeq proteins (3): NP_001305433, NP_001339102, NP_113666* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006634	TLC-dom	Domain
IPR050846	TLCD	Family

Pfam: PF03798

Catalyzed reactions (Rhea), 3 shown:

• sphing-4-enine + hexadecanoyl-CoA = N-hexadecanoylsphing-4-enine + CoA + H(+) (RHEA:36687)
• sphing-4-enine + octadecanoyl-CoA = N-octadecanoylsphing-4-enine + CoA + H(+) (RHEA:36691)
• eicosanoyl-CoA + sphing-4-enine = N-eicosanoyl-sphing-4-enine + CoA + H(+) (RHEA:45284)

UniProt features (8 total): transmembrane region 4, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q71RH2-F1	89.52	0.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GGAMTNNNNNTCCY_UNKNOWN, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, TGCTGAY_UNKNOWN, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, chr16p11

GO Biological Process (4): negative regulation of fat cell differentiation (GO:0045599), ceramide biosynthetic process (GO:0046513), lipid homeostasis (GO:0055088), lipid metabolic process (GO:0006629)

GO Molecular Function (2): sphingosine N-acyltransferase activity (GO:0050291), transferase activity (GO:0016740)

GO Cellular Component (5): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
chemical homeostasis	1
primary metabolic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1013 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLCD3B	SGPP1	Q9BX95	898
TLCD3B	SPHK2	Q9NRA0	880
TLCD3B	SPTLC2	O15270	872
TLCD3B	SPTLC1	O15269	848
TLCD3B	SPTLC3	Q9NUV7	846
TLCD3B	SMPD1	P17405	807
TLCD3B	UBP1	Q9NZI7	763
TLCD3B	CERS2	Q96G23	724
TLCD3B	CERS6	Q6ZMG9	723
TLCD3B	ACSL5	Q9ULC5	703
TLCD3B	SPHK1	Q9NYA1	700
TLCD3B	UGCG	Q16739	667
TLCD3B	CERS5	Q8N5B7	655
TLCD3B	SMPD2	O60906	651
TLCD3B	GDF1	P27539	643

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TLCD3B	RTKN	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): FAM57B (Affinity Capture-MS), RTKN (Affinity Capture-MS)

ESM2 similar proteins: A2AE42, A3A9H6, A5D7C9, A5D9A7, A6NM10, B3SHH9, B5DFH9, B9EJG8, F1NZP5, O14569, P10897, P49447, P82352, Q08DE1, Q14714, Q148G2, Q3ZCD2, Q5E965, Q5ND56, Q5RCZ2, Q5U2W7, Q5ZJX0, Q60720, Q62147, Q641Y1, Q6GPL4, Q6P0C6, Q6P1H1, Q71RH2, Q7TNV1, Q80ZE4, Q86TG1, Q8BMD6, Q8C8S3, Q8IXF9, Q8N8Q1, Q8NBI2, Q8TBR7, Q8VHW3, Q8VHW7

Diamond homologs: Q5ND56, Q71RH2, Q7TNV1, Q8TBR7, Q6AYM9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
propan-2-ol	“up-regulates activity”	TLCD3B	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1268235	NM_031478.6(TLCD3B):c.166G>A (p.Gly56Ser)	Pathogenic
1684552	GRCh37/hg19 16p11.2(chr16:29601322-30201321)x1	Pathogenic
243052	Single allele	Pathogenic

SpliceAI

1086 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30025468:C:CC	acceptor_gain	1.0000
16:30025819:CAC:C	acceptor_gain	1.0000
16:30025820:ACC:A	acceptor_loss	1.0000
16:30025821:CCTGG:C	acceptor_loss	1.0000
16:30025823:T:C	acceptor_loss	1.0000
16:30026604:CTCAC:C	donor_loss	1.0000
16:30026607:A:AC	donor_gain	1.0000
16:30026607:A:T	donor_loss	1.0000
16:30026608:C:CC	donor_gain	1.0000
16:30026608:CCA:C	donor_gain	1.0000
16:30026839:AGTGT:A	acceptor_gain	1.0000
16:30026840:GTGT:G	acceptor_gain	1.0000
16:30026841:TGT:T	acceptor_gain	1.0000
16:30026841:TGTCT:T	acceptor_loss	1.0000
16:30026842:GT:G	acceptor_gain	1.0000
16:30026843:TCT:T	acceptor_loss	1.0000
16:30026844:C:CC	acceptor_gain	1.0000
16:30026844:C:CG	acceptor_loss	1.0000
16:30026845:T:A	acceptor_loss	1.0000
16:30029428:TTACT:T	donor_loss	1.0000
16:30029429:TAC:T	donor_loss	1.0000
16:30029430:A:AC	donor_gain	1.0000
16:30029431:C:CC	donor_gain	1.0000
16:30029431:CT:C	donor_gain	1.0000
16:30029431:CTG:C	donor_gain	1.0000
16:30029431:CTGG:C	donor_gain	1.0000
16:30029431:CTGGT:C	donor_gain	1.0000
16:30029511:CCAGC:C	acceptor_gain	1.0000
16:30029512:CAGCC:C	acceptor_gain	1.0000
16:30025463:TTGTA:T	acceptor_gain	0.9900

AlphaMissense

1769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30025408:G:C	F200L	1.000
16:30025408:G:T	F200L	1.000
16:30025410:A:G	F200L	1.000
16:30025762:G:C	S168R	1.000
16:30025762:G:T	S168R	1.000
16:30025764:T:G	S168R	1.000
16:30026650:G:C	H135D	1.000
16:30026790:T:A	D88V	1.000
16:30026790:T:G	D88A	1.000
16:30025409:A:G	F200S	0.999
16:30025411:G:C	S199R	0.999
16:30025411:G:T	S199R	0.999
16:30025413:T:G	S199R	0.999
16:30025430:C:T	G193E	0.999
16:30025432:G:C	N192K	0.999
16:30025432:G:T	N192K	0.999
16:30025749:A:G	C173R	0.999
16:30025751:A:T	V172D	0.999
16:30025757:G:T	P170H	0.999
16:30025769:T:A	E166V	0.999
16:30026645:A:C	H136Q	0.999
16:30026645:A:T	H136Q	0.999
16:30026647:G:C	H136D	0.999
16:30026647:G:T	H136N	0.999
16:30026650:G:T	H135N	0.999
16:30026777:C:A	M92I	0.999
16:30026777:C:G	M92I	0.999
16:30026777:C:T	M92I	0.999
16:30026789:G:C	D88E	0.999
16:30026789:G:T	D88E	0.999

dbSNP variants (sampled 300 via entrez): RS1000238332 (16:30049750 C>A,G), RS1000318863 (16:30024907 C>T), RS1000329433 (16:30043063 G>A,T), RS1000343324 (16:30044344 G>GT), RS1000401387 (16:30042758 T>A,C), RS1000533390 (16:30036326 A>G), RS1000590226 (16:30050063 T>G), RS1000715306 (16:30029706 G>A,T), RS1000746923 (16:30029538 C>A), RS1000747649 (16:30039398 C>T), RS1000967873 (16:30035969 G>T), RS1000992377 (16:30032571 C>A), RS1001382820 (16:30046678 C>A), RS1001457717 (16:30043475 A>G), RS1001483520 (16:30045129 G>A,C,T)

Disease associations

OMIM: gene MIM:615175 | disease phenotypes: MIM:619531, MIM:122600

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy 22	Strong	Autosomal recessive
cone-rod dystrophy	Supportive	Autosomal dominant

Mondo (3): cone-rod dystrophy 22 (MONDO:0030440), spondylocostal dysostosis 5 (MONDO:0007389), cone-rod dystrophy (MONDO:0015993)

Orphanet (0):

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0003621	Juvenile onset
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007722	Retinal pigment epithelial atrophy
HP:0007737	Spicular pigmentation of the retina
HP:0007843	Attenuation of retinal blood vessels
HP:0011462	Young adult onset
HP:0011504	Bull’s eye maculopathy
HP:0012508	Metamorphopsia
HP:0025159	Hypoautofluorescent retinal lesion
HP:0030466	Abnormal full-field electroretinogram
HP:0030629	Perifoveal ring of hyperautofluorescence
HP:0030631	Hyperautofluorescent macular lesion
HP:0030825	Absent foveal reflex
HP:0030844	Undetectable pattern electroretinogram

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002539_82	Schizophrenia	5.000000e-11
GCST004521_236	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST004600_133	Eosinophil percentage of white cells	2.000000e-13
GCST004617_113	Eosinophil percentage of granulocytes	2.000000e-13
GCST004623_77	Neutrophil percentage of granulocytes	6.000000e-12
GCST004946_142	Schizophrenia	8.000000e-13
GCST006803_23	Schizophrenia	6.000000e-13
GCST007293_15	Body fat distribution (arm fat ratio)	6.000000e-06
GCST007293_81	Body fat distribution (arm fat ratio)	4.000000e-08
GCST007611_22	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	7.000000e-09
GCST009379_164	Type 2 diabetes	2.000000e-09
GCST009379_165	Type 2 diabetes	1.000000e-06
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13
GCST90000025_89	Appendicular lean mass	6.000000e-46

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Valproic Acid	affects expression, increases methylation	2
ethyl-p-hydroxybenzoate	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Estradiol	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases methylation	1
Lactic Acid	increases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00427180	Not specified	UNKNOWN	IRIS PILOT - Extended Pilot Study With a Retinal Implant System
NCT01864486	Not specified	COMPLETED	Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02670980	Not specified	COMPLETED	Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance