Mutagenetix > Incidental Mutation

Incidental Mutation 'R6218:Ddhd1'

503864

Institutional Source

Beutler Lab

Gene Symbol

Ddhd1

Ensembl Gene

ENSMUSG00000037697

Gene Name

DDHD domain containing 1

Synonyms

9630061G18Rik, 4921528E07Rik

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6218 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

45588467-45658143 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 45614176 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 141 (L141P)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000051310] [ENSMUST00000087320] [ENSMUST00000111828] [ENSMUST00000149286]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000051310
AA Change: L481P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000050088
Gene: ENSMUSG00000037697
AA Change: L481P

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
low complexity region	95	111	N/A	INTRINSIC
low complexity region	118	141	N/A	INTRINSIC
low complexity region	183	201	N/A	INTRINSIC
low complexity region	206	217	N/A	INTRINSIC
low complexity region	284	297	N/A	INTRINSIC
Blast:DDHD	450	573	6e-67	BLAST
DDHD	595	842	1.49e-100	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000087320
AA Change: L515P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000084577
Gene: ENSMUSG00000037697
AA Change: L515P

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
low complexity region	95	111	N/A	INTRINSIC
low complexity region	118	141	N/A	INTRINSIC
low complexity region	183	201	N/A	INTRINSIC
low complexity region	206	217	N/A	INTRINSIC
low complexity region	284	297	N/A	INTRINSIC
Blast:DDHD	484	607	1e-66	BLAST
DDHD	629	904	3.75e-106	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000111828
AA Change: L481P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000107459
Gene: ENSMUSG00000037697
AA Change: L481P

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
low complexity region	95	111	N/A	INTRINSIC
low complexity region	118	141	N/A	INTRINSIC
low complexity region	183	201	N/A	INTRINSIC
low complexity region	206	217	N/A	INTRINSIC
low complexity region	284	297	N/A	INTRINSIC
Blast:DDHD	450	573	8e-67	BLAST
DDHD	595	870	3.75e-106	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126428

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129599

Predicted Effect

probably damaging
Transcript: ENSMUST00000141487
AA Change: L141P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000133358
Gene: ENSMUSG00000037697
AA Change: L141P

Domain	Start	End	E-Value	Type
Blast:DDHD	111	149	1e-17	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000149286

SMART Domains

Protein: ENSMUSP00000118848
Gene: ENSMUSG00000037697

Domain	Start	End	E-Value	Type
low complexity region	28	39	N/A	INTRINSIC
low complexity region	95	111	N/A	INTRINSIC
low complexity region	118	141	N/A	INTRINSIC
low complexity region	183	201	N/A	INTRINSIC
low complexity region	206	217	N/A	INTRINSIC
low complexity region	284	297	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000152110

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227258

Meta Mutation Damage Score

0.6701

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.5%

Validation Efficiency

100% (65/65)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the intracellular phospholipase A1 gene family. The protein encoded by this gene preferentially hydrolyzes phosphatidic acid. It is a cytosolic protein with some mitochondrial localization, and is thought to be involved in the regulation of mitochondrial dynamics. Overexpression of this gene causes fragmentation of the tubular structures in mitochondria, while depletion of the gene results in mitochondrial tubule elongation. Deletion of this gene in male mice caused fertility defects, resulting from disruption in the organization of the mitochondria during spermiogenesis. In humans, mutations in this gene have been associated with hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain disease, or, familial spastic paraparesis (FSP). This inherited disorder is characterized by progressive weakness and spasticity of the legs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
PHENOTYPE: Mice homozygous for a null allele show reduced testis weight, oligozoospermia, teratozoospermia, and male subfertility. Sperm defects include a disorganized mitochondrial structure, an abnormal gap between the middle and principal pieces, and hairpin flagellum leading to impaired sperm motility. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2300003K06Rik	G	T	11: 99,837,904	Q38K	probably benign	Het
9930111J21Rik2	A	T	11: 49,019,307	N766K	probably benign	Het
Adam15	A	C	3: 89,343,883	I505S	probably benign	Het
Apc2	T	C	10: 80,306,420	M391T	probably damaging	Het
Arsi	G	A	18: 60,916,651	G202E	probably benign	Het
Bclaf1	A	G	10: 20,334,628	S840G	probably benign	Het
Cacna2d4	A	G	6: 119,239,060	Y96C	probably damaging	Het
Cald1	CAAAA	CAAA	6: 34,747,928		probably null	Het
Dnaaf3	A	T	7: 4,523,672	S469T	probably benign	Het
Dzip3	A	T	16: 48,958,465	M323K	possibly damaging	Het
E430018J23Rik	C	T	7: 127,393,409	A10T	possibly damaging	Het
Eci2	T	A	13: 34,993,065		probably null	Het
Fam109b	T	A	15: 82,343,716	H145Q	probably benign	Het
Fam227b	A	T	2: 126,126,962	V64E	probably damaging	Het
Galnt2	A	G	8: 124,343,315	I524V	probably benign	Het
Gm10549	C	A	18: 33,464,305		probably benign	Het
Gm14548	A	T	7: 3,894,032	S602T	possibly damaging	Het
Gm3443	T	A	19: 21,555,746	S25T	probably damaging	Het
Gpr22	T	A	12: 31,711,617	K14*	probably null	Het
Grip1	T	C	10: 119,986,346	S405P	possibly damaging	Het
Helz2	C	A	2: 181,232,294	V2136L	probably benign	Het
Helz2	T	C	2: 181,235,945	H1020R	probably damaging	Het
Il1f5	G	A	2: 24,277,490		probably benign	Het
Iqsec1	T	A	6: 90,689,635	S607C	probably damaging	Het
Klhl2	A	T	8: 64,752,767	Y373*	probably null	Het
L3mbtl3	T	C	10: 26,292,747	I595V	unknown	Het
Large2	T	C	2: 92,370,636	D65G	probably damaging	Het
Lrrfip1	T	C	1: 91,082,159	Y122H	probably damaging	Het
Map1b	A	T	13: 99,433,206	D1002E	unknown	Het
Mink1	C	T	11: 70,598,894	T59I	possibly damaging	Het
Mrvi1	G	A	7: 110,876,905	T819M	probably benign	Het
Myo7b	T	C	18: 31,959,454	N2097D	probably benign	Het
Nbea	C	A	3: 55,628,484	C2893F	probably damaging	Het
Nlgn1	A	T	3: 25,436,093	V490E	probably damaging	Het
Olfr1230	G	T	2: 89,296,962	H103N	probably damaging	Het
Olfr131	A	G	17: 38,082,729	M83T	probably damaging	Het
Olfr1318	T	C	2: 112,156,356	I135T	probably damaging	Het
Olfr1369-ps1	G	A	13: 21,116,231	E180K	probably damaging	Het
Olfr730	C	A	14: 50,186,678	D180Y	probably damaging	Het
Pctp	A	G	11: 89,987,318	I130T	probably benign	Het
Pdcl3	T	C	1: 38,988,071		probably null	Het
Pkp1	T	C	1: 135,879,908	K541E	probably damaging	Het
Plekhh2	G	A	17: 84,591,564	V990I	probably benign	Het
Ppp1r3a	A	T	6: 14,718,431	V828D	probably damaging	Het
Prrc2b	T	C	2: 32,208,811	Y712H	probably damaging	Het
Prune2	T	C	19: 17,121,562	S1477P	probably benign	Het
Psma5	A	G	3: 108,279,802	K239R	probably benign	Het
Rhobtb1	G	C	10: 69,270,456	A284P	probably benign	Het
Samsn1	G	A	16: 75,945,274		noncoding transcript	Het
Scel	A	G	14: 103,572,042	T273A	probably benign	Het
Slc22a5	T	A	11: 53,891,618		probably benign	Het
Slc25a37	A	T	14: 69,249,504	M110K	possibly damaging	Het
Slc6a2	A	T	8: 92,981,981	M242L	probably benign	Het
Slc8a3	C	A	12: 81,199,567	W904L	probably benign	Het
Ss18l1	G	A	2: 180,055,112	V109I	probably benign	Het
Tbx5	C	T	5: 119,853,598	H245Y	probably damaging	Het
Thumpd2	C	A	17: 81,052,913	L244F	probably damaging	Het
Tmem107	T	A	11: 69,071,415	V66E	probably damaging	Het
Tnr	T	C	1: 159,888,314	V882A	possibly damaging	Het
Top2b	T	G	14: 16,409,189	I777M	probably damaging	Het
Ttbk1	A	G	17: 46,470,807	V340A	possibly damaging	Het
Veph1	T	C	3: 66,255,060	E59G	probably damaging	Het
Vmn1r234	T	A	17: 21,229,721	M299K	possibly damaging	Het
Vps13b	T	C	15: 35,770,464	Y2018H	probably benign	Het
Zbtb11	A	G	16: 55,998,073	E620G	probably benign	Het
Zfp418	A	G	7: 7,182,628	H530R	possibly damaging	Het

Other mutations in Ddhd1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01318:Ddhd1	APN	14	45616551	missense	probably damaging	1.00
IGL01635:Ddhd1	APN	14	45629580	missense	probably null	0.98
IGL02176:Ddhd1	APN	14	45616600	missense	probably damaging	1.00
IGL02698:Ddhd1	APN	14	45605206	unclassified	probably benign
IGL03052:Ddhd1	UTSW	14	45620783	missense	probably damaging	1.00
PIT4434001:Ddhd1	UTSW	14	45610605	missense	possibly damaging	0.62
R0037:Ddhd1	UTSW	14	45610510	missense	probably damaging	1.00
R0105:Ddhd1	UTSW	14	45610690	missense	probably benign	0.37
R0165:Ddhd1	UTSW	14	45595592	missense	probably damaging	1.00
R1237:Ddhd1	UTSW	14	45601650	missense	probably benign	0.01
R1401:Ddhd1	UTSW	14	45605051	critical splice donor site	probably null
R1574:Ddhd1	UTSW	14	45595547	missense	probably damaging	1.00
R1574:Ddhd1	UTSW	14	45595547	missense	probably damaging	1.00
R1582:Ddhd1	UTSW	14	45605109	missense	probably damaging	0.98
R2070:Ddhd1	UTSW	14	45610624	missense	probably damaging	1.00
R2307:Ddhd1	UTSW	14	45608990	missense	probably damaging	1.00
R2417:Ddhd1	UTSW	14	45657272	missense	probably damaging	1.00
R3756:Ddhd1	UTSW	14	45610573	missense	probably benign	0.00
R3756:Ddhd1	UTSW	14	45657263	missense	probably damaging	1.00
R4541:Ddhd1	UTSW	14	45622856	nonsense	probably null
R4737:Ddhd1	UTSW	14	45628821	intron	probably benign
R5105:Ddhd1	UTSW	14	45657407	missense	probably benign	0.00
R5810:Ddhd1	UTSW	14	45602707	missense	probably damaging	1.00
R5898:Ddhd1	UTSW	14	45602668	missense	probably damaging	1.00
R6217:Ddhd1	UTSW	14	45619514	splice site	probably null
R6671:Ddhd1	UTSW	14	45657232	frame shift	probably null
R6787:Ddhd1	UTSW	14	45657519	missense	probably benign	0.01
R7049:Ddhd1	UTSW	14	45602681	missense	probably damaging	1.00
R7150:Ddhd1	UTSW	14	45657806	missense	probably damaging	1.00
R7213:Ddhd1	UTSW	14	45657753	missense	probably benign	0.41
R7261:Ddhd1	UTSW	14	45657231	missense	probably damaging	1.00
R7522:Ddhd1	UTSW	14	45657647	missense	possibly damaging	0.47
R7920:Ddhd1	UTSW	14	45657470	missense	probably damaging	0.96
R8736:Ddhd1	UTSW	14	45599185	missense	probably benign	0.30
R8880:Ddhd1	UTSW	14	45608973	missense	probably benign
R9140:Ddhd1	UTSW	14	45657461	missense	probably benign	0.12
R9393:Ddhd1	UTSW	14	45657228	missense	probably damaging	1.00
R9398:Ddhd1	UTSW	14	45657660	missense	possibly damaging	0.60
R9399:Ddhd1	UTSW	14	45657660	missense	possibly damaging	0.60
R9502:Ddhd1	UTSW	14	45657222	missense	possibly damaging	0.75
R9687:Ddhd1	UTSW	14	45610733	missense	probably damaging	0.97
Z1177:Ddhd1	UTSW	14	45657594	missense	possibly damaging	0.63

Predicted Primers

PCR Primer
(F):5'- TTCCTGAGTGTGGGACTAAAGG -3'
(R):5'- CCCCACTGGTGTTTAATATTTCAGTAG -3'

Sequencing Primer
(F):5'- ACTAAAGGTGTGCCCTGC -3'
(R):5'- TTCAGTAGTGACCTCTGTAACTG -3'

Posted On

2018-02-27