DYTN

Summary

DYTN (dystrotelin, HGNC:23279) is a protein-coding gene on chromosome 2q33.3, encoding Dystrotelin (A2CJ06).

This gene belongs to the dystrophin superfamily, which is characterized by the presence of four EF-hand motifs and a ZZ-domain. It is a likely ortholog of the Drosophila ‘discontinuous actin hexagon’ gene. It is noteworthy that the coding region of this gene lacks two coding exons that are found in the mouse ortholog. Human transcripts including these two exons are subject to nonsense-mediated transcript decay (NMD). On the other hand, transcripts skipping the two coding exons are expressed at very low levels. While this gene maintains an intact CDS, it may be an evolving pseudogene. However, after a discussion about this gene within the RefSeq group, as well as in the consensus coding sequence (CCDS) collaboration, it was decided to keep it as a protein-coding gene in the RefSeq, Ensembl-GENCODE and the CCDS sets.

Source: NCBI Gene 391475 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001093730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23279
Approved symbol	DYTN
Name	dystrotelin
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000232125
Ensembl biotype	protein_coding
OMIM	618510
Entrez	391475

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000452335, ENST00000477734, ENST00000674258

RefSeq mRNA: 1 — MANE Select: NM_001093730 NM_001093730

CCDS: CCDS46502

Canonical transcript exons

ENST00000452335 — 12 exons

Exon	Start	End
ENSE00001649591	206718261	206718396
ENSE00001659171	206707302	206707503
ENSE00001662768	206693175	206693323
ENSE00001683394	206662903	206663395
ENSE00001685928	206665870	206666029
ENSE00001693013	206651621	206651921
ENSE00001711376	206704843	206704943
ENSE00001762827	206705788	206705873
ENSE00001788992	206694766	206694877
ENSE00001803795	206710524	206710598
ENSE00003559190	206700145	206700216
ENSE00003690509	206699727	206699890

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 79.76.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.76	silver quality
monocyte	CL:0000576	67.25	gold quality
leukocyte	CL:0000738	66.40	gold quality
blood	UBERON:0000178	52.55	gold quality
granulocyte	CL:0000094	51.58	gold quality
bone marrow	UBERON:0002371	50.22	silver quality
bone marrow cell	CL:0002092	48.45	gold quality
right lung	UBERON:0002167	37.65	silver quality
lower esophagus mucosa	UBERON:0035834	37.60	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
spleen	UBERON:0002106	36.94	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
sural nerve	UBERON:0015488	35.59	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.94	gold quality
right uterine tube	UBERON:0001302	33.73	gold quality
muscle tissue	UBERON:0002385	33.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
fallopian tube	UBERON:0003889	31.56	silver quality
Brodmann (1909) area 9	UBERON:0013540	30.98	gold quality
upper lobe of left lung	UBERON:0008952	30.79	gold quality
superior frontal gyrus	UBERON:0002661	29.92	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
lung	UBERON:0002048	29.77	silver quality
islet of Langerhans	UBERON:0000006	29.57	gold quality
left uterine tube	UBERON:0001303	29.52	gold quality
putamen	UBERON:0001874	29.30	gold quality
liver	UBERON:0002107	29.12	gold quality
Ammon’s horn	UBERON:0001954	28.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting DYTN, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-649	97.96	67.21	704
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-4683	95.29	65.98	631

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dytn	ENSDARG00000071025
mus_musculus	Dytn	ENSMUSG00000069085
rattus_norvegicus	Dytn	ENSRNOG00000042181

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Dystrotelin — A2CJ06 (reviewed: A2CJ06)

All UniProt accessions (2): A2CJ06, A0A590UJG6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

RefSeq proteins (1): NP_001087199* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000433	Znf_ZZ	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR015153	EF-hand_dom_typ1	Domain
IPR015154	EF-hand_dom_typ2	Domain
IPR043145	Znf_ZZ_sf	Homologous_superfamily
IPR050774	KCMF1/Dystrophin	Family

Pfam: PF00569, PF09068, PF09069

UniProt features (18 total): binding site 8, compositionally biased region 3, sequence variant 2, coiled-coil region 2, chain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2CJ06-F1	69.89	0.29

Functional residue map

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

Ligand- & substrate-binding residues (8): 243; 246; 252; 255; 265; 269; 228; 231

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 19 (showing top): GOBP_CELL_CELL_SIGNALING, GOBP_SYNAPTIC_SIGNALING, GOCC_SYNAPSE, GSE14415_TCONV_VS_FOXP3_KO_INDUCED_TREG_UP, ZNF322_TARGET_GENES, ZNF486_TARGET_GENES, MANNE_COVID19_NONICU_VS_HEALTHY_DONOR_PLATELETS_DN, MANNE_COVID19_ICU_VS_HEALTHY_DONOR_PLATELETS_DN, MANNE_COVID19_COMBINED_COHORT_VS_HEALTHY_DONOR_PLATELETS_DN, DESCARTES_MAIN_FETAL_HEMATOPOIETIC_STEM_CELLS, DESCARTES_FETAL_CEREBELLUM_GRANULE_NEURONS, DESCARTES_FETAL_CEREBRUM_MEGAKARYOCYTES, ZNF260_TARGET_GENES, HE_LIM_SUN_FETAL_LUNG_C2_HSC_CELL, GSE5589_WT_VS_IL6_KO_LPS_STIM_MACROPHAGE_180MIN_DN

GO Biological Process (1): synaptic signaling (GO:0099536)

GO Molecular Function (2): zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (3): plasma membrane (GO:0005886), synapse (GO:0045202), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell signaling	1
synapse	1
transition metal ion binding	1
cation binding	1
membrane	1
cell periphery	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYTN	FASTKD2	Q9NYY8	608
DYTN	OR3A2	P47893	480
DYTN	MIER3	Q7Z3K6	441
DYTN	ADAM23	O75077	410
DYTN	DYNLT5	Q8N7M0	403
DYTN	ACHE	P22303	393
DYTN	MDH1B	Q5I0G3	393
DYTN	PTDSS2	Q9BVG9	385
DYTN	RAB11FIP4	Q86YS3	379
DYTN	LRRC38	Q5VT99	377
DYTN	VPS26C	O14972	373
DYTN	CCNYL1	Q8N7R7	372
DYTN	KLF7	O75840	369
DYTN	CARF	Q8N187	369
DYTN	ADAM28	Q9UKQ2	353
DYTN	NOS1AP	O75052	353

IntAct

0 interactions, top by confidence:

BioGRID (2): DYTN (Affinity Capture-MS), KIDINS220 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GUJ8, A1A5R7, A2CJ06, A7E3N2, B1H224, B8QB46, D3Z8Y2, D3ZSP7, O55036, P0CG32, P54274, P70371, Q14BQ3, Q29RJ0, Q2HJ46, Q2T9U5, Q3TTP0, Q4R8X0, Q4R9F7, Q4VA55, Q5DTT8, Q5RBH9, Q5TKR9, Q5U310, Q5ZIX8, Q6DJS0, Q6ZQF7, Q71M44, Q7Z2W4, Q7Z7J5, Q80VH0, Q80VM8, Q8BMD7, Q8BZ21, Q8CCG4, Q8CDN1, Q8JZW8, Q8ND61, Q8TE76, Q8VD24

Diamond homologs: A2CI97, A2CI98, A2CJ06, G3V7L1, O97592, P11530, P11531, P11532, P11533, P46939, Q05AA6, Q0KI50, Q13474, Q5GN48, Q7YU29, Q8NEG5, Q9EPA0, Q9TW65, Q9VDW3, Q9VDW6, Q9Y4J8, O70585, P84060, Q9D2N4, Q9P792, O60941, Q4U2R1, Q9VUX2, A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, G3MWR8, L7UZ85, M9MRD1, O13728, O15020

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2463 predictions. Top by Δscore:

Variant	Effect	Δscore
2:206665887:T:C	donor_gain	1.0000
2:206707504:C:CC	acceptor_gain	1.0000
2:206718257:TCAC:T	donor_loss	1.0000
2:206718258:CACCT:C	donor_loss	1.0000
2:206718259:A:AC	donor_gain	1.0000
2:206718259:AC:A	donor_gain	1.0000
2:206718260:C:CC	donor_gain	1.0000
2:206718260:C:CT	donor_loss	1.0000
2:206718260:CC:C	donor_gain	1.0000
2:206718260:CCT:C	donor_gain	1.0000
2:206718260:CCTT:C	donor_gain	1.0000
2:206662896:ACCTT:A	donor_loss	0.9900
2:206662897:CCTTA:C	donor_loss	0.9900
2:206662898:CTTA:C	donor_loss	0.9900
2:206662899:TTA:T	donor_loss	0.9900
2:206662900:T:TA	donor_loss	0.9900
2:206662901:A:AA	donor_loss	0.9900
2:206662902:CC:C	donor_loss	0.9900
2:206663391:CTTGC:C	acceptor_gain	0.9900
2:206663396:C:CC	acceptor_gain	0.9900
2:206670474:A:AC	donor_gain	0.9900
2:206670475:C:CC	donor_gain	0.9900
2:206694883:A:T	acceptor_gain	0.9900
2:206707501:CCA:C	acceptor_gain	0.9900
2:206707502:CA:C	acceptor_gain	0.9900
2:206707502:CAC:C	acceptor_gain	0.9900
2:206710523:CA:C	donor_gain	0.9900
2:206712985:T:C	acceptor_gain	0.9900
2:206718260:CCTTG:C	donor_gain	0.9900
2:206651922:C:CC	acceptor_gain	0.9800

AlphaMissense

3788 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:206700151:G:C	F183L	0.966
2:206700151:G:T	F183L	0.966
2:206700153:A:G	F183L	0.966
2:206704936:A:C	F130L	0.959
2:206704936:A:T	F130L	0.959
2:206704938:A:G	F130L	0.959
2:206699821:A:G	W209R	0.952
2:206699821:A:T	W209R	0.952
2:206699858:G:C	F196L	0.943
2:206699858:G:T	F196L	0.943
2:206699860:A:G	F196L	0.943
2:206707388:A:C	F70L	0.939
2:206707388:A:T	F70L	0.939
2:206707390:A:G	F70L	0.939
2:206705795:T:A	K125N	0.926
2:206705795:T:G	K125N	0.926
2:206699851:A:G	W199R	0.924
2:206699851:A:T	W199R	0.924
2:206699859:A:G	F196S	0.920
2:206700152:A:G	F183S	0.919
2:206651860:G:C	F565L	0.918
2:206651860:G:T	F565L	0.918
2:206651862:A:G	F565L	0.918
2:206700156:A:G	C182R	0.907
2:206710552:T:A	K22N	0.903
2:206710552:T:G	K22N	0.903
2:206700154:A:C	C182W	0.902
2:206699849:C:A	W199C	0.901
2:206699849:C:G	W199C	0.901
2:206704886:A:G	M147T	0.889

dbSNP variants (sampled 300 via entrez): RS1000004781 (2:206699456 A>G), RS1000015628 (2:206702621 C>T), RS1000128626 (2:206696277 C>G), RS1000134728 (2:206655983 T>C), RS1000159205 (2:206702474 G>A), RS1000162553 (2:206680112 AAAG>A), RS1000269658 (2:206684400 A>C), RS1000273131 (2:206708555 G>A), RS1000276491 (2:206702274 C>T), RS1000278853 (2:206668754 C>T), RS1000293849 (2:206662410 C>T), RS1000352851 (2:206674245 G>A), RS1000372324 (2:206707690 T>G), RS1000572441 (2:206719990 G>A), RS1000604425 (2:206657379 A>G)

Disease associations

OMIM: gene MIM:618510 | 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
GCST003079_1	Cerebrospinal fluid t-tau:AB1-42 ratio	4.000000e-07
GCST005951_45	Body mass index	1.000000e-09
GCST010142_77	Fish- and plant-related diet	2.000000e-08
GCST012616_21	Spondylosis	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0004340	body mass index
EFO:0008111	diet measurement

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
Fulvestrant	increases methylation	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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